Substituted pyridine compounds and methods of use

ABSTRACT

Selected novel substituted pyridine compounds are effective for prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

This application claims priority from Provisional Application number 60/064,953, filed Nov. 7, 1997.

BACKGROUND OF THE INVENTION

The present invention comprises a new class of compounds useful in treating diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases and other maladies, such as pain, cancer, and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. This invention also relates to intermediates and processes useful in the preparation of such compounds.

Interleukin-1 (IL-1) and Tumor Necrosis Factor α (TNF-α) are pro-inflammatory cytokines secreted by a variety of cells, including monocytes and macrophages, in response to many inflammatory stimuli (e.g., lipopolysaccharide--LPS) or external cellular stress (e.g., osmotic shock and peroxide).

Elevated levels of TNF-α and/or IL-1 over basal levels have been implicated in mediating or exacerbating a number of disease states including rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; graft vs. host reaction; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection. HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), and herpes zoster are also exacerbated by TNF-α.

It has been reported that TNF-α plays a role in head trauma, stroke, and ischemia. For instance, in animal models of head trauma (rat), TNF-α levels increased in the contused hemisphere (Shohami et al., J. Cereb. Blood Flow Metab. 14, 615 (1994)). In a rat model of ischemia wherein the middle cerebral artery was occluded, the levels of TNF-α MRNA of TNF-α increased (Feurstein et al., Neurosci. Lett. 164, 125 (1993)). Administration of TNF-α into the rat cortex has been reported to result in significant neutrophil accumulation in capillaries and adherence in small blood vessels. TNF-α promotes the infiltration of other cytokines (IL-1β, IL-6) and also chemokines, which promote neutrophil infiltration into the infarct area (Feurstein, Stroke 25, 1481 (1994)). TNF-α has also been implicated to play a role in type II diabetes (Endocrinol. 130, 43-52, 1992; and Endocrinol. 136, 1474-1481, 1995).

TNF-α appears to play a role in promoting certain viral life cycles and disease states associated with them. For instance, TNF-α secreted by monocytes induced elevated levels of HIV expression in a chronically infected T cell clone (Clouse et al., J. Immunol. 142, 431 (1989)). Lahdevirta et al., (Am. J. Med. 85, 289 (1988)) discussed the role of TNF-α in the HIV associated states of cachexia and muscle degradation.

TNF-α is upstream in the cytokine cascade of inflammation. As a result, elevated levels of TNF-α may lead to elevated levels of other inflammatory and proinflammatory cytokines, such as IL-1, IL-6, and IL-8.

Elevated levels of IL-1 over basal levels have been implicated in mediating or exacerbating a number of disease states including rheumatoid arthritis; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; ulcerative colitis; anaphylaxis; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; sepsis; septic shock; and toxic shock syndrome. Viruses sensitive to TNF-α inhibition, e.g., HIV-1, HIV-2, HIV-3, are also affected by IL-1.

TNF-α and IL-1 appear to play a role in pancreatic β cell destruction and diabetes. Pancreatic β cells produce insulin which helps mediate blood glucose homeostasis. Deterioration of pancreatic β cells often accompanies type I diabetes. Pancreatic β cell functional abnormalities may occur in patients with type II diabetes. Type II diabetes is characterized by a functional resistance to insulin. Further, type II diabetes is also often accompanied by elevated levels of plasma glucagon and increased rates of hepatic glucose production. Glucagon is a regulatory hormone that attenuates liver gluconeogenesis inhibition by insulin. Glucagon receptors have been found in the liver, kidney and adipose tissue. Thus glucagon antagonists are useful for attenuating plasma glucose levels (WO 97/16442, incorporated herein by reference in its entirety). By antagonizing the glucagon receptors, it is thought that insulin responsiveness in the liver will improve, thereby decreasing gluconeogenesis and lowering the rate of hepatic glucose production.

In rheumatoid arthritis models in animals, multiple intra-articular injections of IL-1 have led to an acute and destructive form of arthritis (Chandrasekhar et al., Clinical Immunol Immunopathol. 55, 382 (1990)). In studies using cultured rheumatoid synovial cells, IL-1 is a more potent inducer of stromelysin than is TNF-α (Firestein, Am. J. Pathol. 140, 1309 (1992)). At sites of local injection, neutrophil, lymphocyte, and monocyte emigration has been observed. The emigration is attributed to the induction of chemokines (e.g., IL-8), and the up-regulation of adhesion molecules (Dinarello, Eur. Cytokine Netw. 5, 517-531 (1994)).

IL-1 also appears to play a role in promoting certain viral life cycles. For example, cytokine-induced increase of HIV expression in a chronically infected macrophage line has been associated with a concomitant and selective increase in IL-1 production (Folks et al., J. Immunol. 136, 4049 (1986)). Beutler et al. (J. Immunol. 135, 3969 (1985)) discussed the role of IL-1 in cachexia. Baracos et al. (New Eng. J. Med. 308, 553 (1983)) discussed the role of IL-1 in muscle degeneration.

In rheumatoid arthritis, both IL-1 and TNF-α induce synoviocytes and chondrocytes to produce collagenase and neutral proteases, which leads to tissue destruction within the arthritic joints. In a model of arthritis (collagen-induced arthritis (CIA) in rats and mice), intra-articular administration of TNF-α either prior to or after the induction of CIA led to an accelerated onset of arthritis and a more severe course of the disease (Brahn et al., Lymphokine Cytokine Res. 11, 253 (1992); and Cooper, Clin. Exp. Immunol. 898, 244 (1992)).

IL-8 has been implicated in exacerbating and/or causing many disease states in which massive neutrophil infiltration into sites of inflammation or injury (e.g., ischemia) is mediated by the chemotactic nature of IL-8, including, but not limited to, the following: asthma, inflammatory bowel disease, psoriasis, adult respiratory distress syndrome, cardiac and renal reperfusion injury, thrombosis and glomerulonephritis. In addition to the chemotaxis effect on neutrophils, IL-8 also has the ability to activate neutrophils. Thus, reduction in IL-8 levels may lead to diminished neutrophil infiltration.

Several approaches have been taken to block the effect of TNF-α. One approach involves using soluble receptors for TNF-α (e.g., TNFR-55 or TNFR-75), which have demonstrated efficacy in animal models of TNF-α-mediated disease states. A second approach to neutralizing TNF-α using a monoclonal antibody specific to TNF-α, cA2, has demonstrated improvement in swollen joint count in a Phase II human trial of rheumatoid arthritis (Maini et al., Immunological Reviews, pp. 195-223 (1995)). These approaches block the effects of TNF-α and IL-1 by either protein sequestration or receptor antagonism.

The present invention also relates to a method of treating cancer which is mediated by Raf and Raf-inducable proteins. Raf proteins are kinases activated in response to extracellular mitogenic stimuli such as PDGF, EGF, acidic FGF, thrombin, insulin or endothelin, and also in response to oncoproteins such as v-src, v-sis, and v-fms. Raf functions downstream of ras in signal transduction from the cellular membrane to the nucleus. Compounds in the present invention may be oncolytics through the antagonism of Raf kinase. Antisense constructs which reduce cellular levels of c-Raf and hence Raf activity inhibit the growth of rodent fibroblasts in soft agar, while exhibiting little or no general cytotoxicity. This inhibition of growth in soft agar is highly predictive of tumor responsiveness in whole animals. Moreover Raf antisense constructs have shown efficacy in reducing tumor burden in animals. Examples of cancers where Raf kinase is implicated by overexpression include cancers of the brain, larynx, lung, lymphatic system, urinary tract and stomach, including hystocytic lymphoma, lung adenocarcinoma and small cell lung cancers. Other examples include cancers involving overexpression of upstream activators of Raf or Raf-activating oncogenes, including pancreatic and breast carcinoma.

Substituted imidazole and pyrrole compounds have been described for use in the treatment of cytokine mediated diseases by inhibition of proinflammatory cytokines, such as IL-1, IL-6, IL-8 and TNF. Substituted imidazoles for use in the treatment of cytokine mediated diseases have been described in U.S. Pat. No. 5,593,992; WO 93/14081; WO 97/18626; WO 96/21452; WO 96/21654; WO 96/40143; WO 97/05878; WO 97/05878; (each of which is incorporated herein by reference in its entirety). Substituted imidazoles for use in the treatment of inflammation has been described in U.S. Pat. No. 3,929,807 (which is incorporated herein by reference in its entirety). Substituted pyrrole compounds for use in the treatment of cytokine mediated diseases have been described in WO 97/05877; WO 97/05878; WO 97/16426; WO 97/16441; and WO 97/16442 (each of which is incorporated herein by reference in its entirety).

Substituted 2-aminopyridine compounds have been described as nitric oxide synthase inhibitors for use in the treatment of inflammation, neurodegenerative disorders and disorders of gastrointestinal motility in WO 96/18616 and WO 96/18617.

Diaryl substituted pyridine compounds have been described for use in the treatment of inflammation and inflammation related disorders in WO 96/24584 and U.S. Pat. No. 5,596,008.

U.S. Pat. No. 3,980,652, U.S. Pat. No. 3,991,057 and U.S. Pat. No. 4,002,629 describe piperazinyl substituted pyridine compounds for use as anti-inflammatory and cardiovascular agents.

JP 6135934 describes substituted pyridine compounds as phospholipase A2 inhibitors for use as antiphlogistic and anti-pancreatitis agents. GB 1,189,188 describes pyrimidin-2-ylamino substituted pyridine compounds as therapeutically valuable compounds for use as antiphlogistic agents.

BRIEF DESCRIPTION OF THE INVENTION

The present invention comprises a new class of compounds useful in the prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases and other maladies, such as pain, cancer, and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds, methods for the prophylaxis and treatment of TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, such as inflammatory, pain and diabetes diseases, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of the compounds of the invention.

The compounds of the invention are represented by the following general structure: ##STR1## wherein R¹, R⁵, R⁶, R⁷, X and Y are defined below.

The foregoing merely summarizes certain aspects of the invention and is not intended, nor should it be construed, as limiting the invention in any way. All patents and other publications recited herein are hereby incorporated by reference in their entirety.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, there is provided compounds of the formula: ##STR2## or a pharmaceutically acceptable salt thereof, wherein X is O, S, S(O) , S(O)₂ or NR² ; preferably, X is O, S or NR² ; more preferably, X is O or NR² ; most preferably, X is NR² ;

Y is --C(O)--NR³ R⁴ or --NR⁴ --C(O)--R³ ;

R¹ is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ -alkyl;

preferably, R¹ is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C₁ -C₆ alkyl, halo, C₁ -C₆ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₆ alkyl;

more preferably, R¹ is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl;

provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R¹ is 1-3, preferably, 1-2, and provided when Y is --NR⁴ --C(O)--R³ and X is O or S, R¹ is other than a 2-pyrimidinyl radical;

more preferably, R¹ is a radical of the formula ##STR3## wherein R²², R²³, R²⁴, R²⁵ and R²⁶ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl; provided at least one of R²¹, R²², R²³, R²⁴ and R²⁵ is hydrogen; and provided that the combined total number of aryl and heteroaryl radicals in R²², R²³, R²⁴, R²⁵ and R²⁶ is 0-1;

R² is a hydrogen or alkyl radical; preferably, R² is a hydrogen or C₁ -C₄ alkyl radical; more preferably, R² is a hydrogen or C₁ -C₂ alkyl radical; more preferably, R² is a hydrogen or methyl radical; and most preferably, R² is a hydrogen radical;

R³ is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ -alkyl; preferably, R³ is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁ -C₆ alkyl, halo, C₁ -C₆ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ --C₁ -C₆ alkyl;

more preferably, R³ is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ --C₁ -C₄ alkyl;

provided that the total number of aryl and heteroaryl radicals in R³ is 1-3, preferably, 1-2; and provided when Y is --C(O)--NR³ R⁴, R³ is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to --NR⁴ --;

more preferably, R³ is a radical of the formula ##STR4## wherein U is C--R¹³ or N;

V and W are each independently C--R¹² or N;

R¹¹ and R¹³ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹ --Z¹⁹ --; preferably, R¹¹ and R¹³ are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹ --O--, R¹⁹ --S(O)₂ --, R¹⁹ --O--C(O)--, R¹⁹ --C(O)--, R¹⁹ --NR²¹ --C(O)-- or R¹⁹ --NR²¹ --S(O)₂ --;

each R¹² is independently a radical of hydrogen, C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, R³¹ --Z³¹ -- or R³¹ --Z³¹ --C₁ -C₄ alkyl; preferably, each R¹² is independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, aminomethyl, (methylamino)methyl or (dimethylamino)methyl;

provided that the combined total number of aryl and heteroaryl radicals in R¹¹, R¹² and R¹³ is 0-1;

wherein each R³¹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

each Z³¹ is independently --O--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --;

R⁴ is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R²⁰ --Z²⁰ -alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, C₂ -C₆ alkenyl, C₁ -C₆ haloalkyl of 1-3 halo radicals, C₂ -C₆ haloalkenyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁ -C₄ alkyl, heteroaryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₁ -C₆ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ --C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, (C₁ -C₄ alkoxy)carbonylamino, (C₁ -C₄ alkoxy)carbonyl, cyano, halo, azido, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals or C₁ -C₄ haloalkoxy of 1-3 halo radicals;

more preferably, R⁴ is a radical of hydrogen, C_(l) -C₆ alkyl, aryl, heteroaryl, aryl-C₁ -C₄ alkyl, heteroaryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₂ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, aryl, heteroaryl, aryl-C₁ -C₄ alkyl, heteroaryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₂ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

more preferably, R⁴ is a radical of hydrogen, methyl or ethyl radical;

wherein each R¹⁸ is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R¹⁸ is independently a hydrogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, (C₁ -C₄ alkoxy)carbonylamino, (C₁ -C₄ alkoxy)carbonyl, cyano, halo, azido, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals or C₁ -C₄ haloalkoxy of 1-3 halo radicals;

more preferably, each R¹⁸ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁ -C₂ alkyl or heteroaryl-C₁ -C₂ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, azido, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy;

each Z¹⁸ is independently --O--, --S--, --S(O)--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; preferably, each Z¹⁸ is independently --O--, --S--, --S(O)₂ --, --CO₂ --, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --;

wherein each R¹⁹ is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, (C₁ -C₄ alkoxy)carbonylamino, (C₁ -C₄ alkoxy)carbonyl, cyano, halo, azido, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals or C₁ -C₄ haloalkoxy of 1-3 halo radicals;

more preferably, each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R¹⁹ is independently a hydrogen, methyl, ethyl, trifluoromethyl, phenyl, heteroaryl, phenylmethyl or heteroaryl-methyl radical, wherein the phenyl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, fluoro, chloro, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

each Z¹⁹ is independently --O--, --S--, --S(O)--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; preferably, each Z¹⁹ is independently --O--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; more preferably, each Z¹⁹ is independently --O--, --S(O)₂ --, --O--C(O)--, --C(O)--, --NR²¹ --C(O)-- or --NR²¹ --S(O)₂ --;

wherein each R²⁰ is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R²⁰ is independently a hydrogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁ -C₄ alkyl or heteroaryl-C₁ -C₄ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, (C₁ -C₄ alkoxy)carbonylamino, (C₁ -C₄ alkoxy)carbonyl, cyano, halo, azido, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals or C₁ -C₄ haloalkoxy of 1-3 halo radicals;

more preferably, each R²⁰ is independently a hydrogen, C₁ -C₄ alkyl, aryl, heteroaryl, aryl-C₁ -C₂ alkyl or heteroaryl-C₁ -C₂ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R²⁰ is independently a hydrogen, C₁ -C₄ alkyl, aryl, heteroaryl, aryl-C₁ -C₂ alkyl or heteroaryl-C₁ -C₂ alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

each Z²⁰ is independently --O--, --S--, --S(O)--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; preferably, each Z²⁰ is independently --O-- or --NR²¹ --;

wherein each R²¹ is independently a hydrogen or alkyl radical; preferably, each R²¹ is independently a hydrogen or C₁ -C₄ alkyl radical; more preferably, each R²¹ is independently a hydrogen or methyl radical;

R⁵ and R⁶ are each independently a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical;

preferably, R⁵ and R⁶ are each independently a hydrogen, C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, C₁ -C₄ haloalkoxy of 1-3 halo radicals, C₁ -C₄ aminoalkyl, (C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, di(C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, aminosulfonyl, C₁ -C₄ alkylaminosulfonyl, di(C₁ --C₄ alkyl)aminosulfonyl, hydroxy, C₁ -C₄ hydroxyalkyl, thiol, C₁ -C₄ alkylthiol, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, C₁ -C₄ alkoxy, (C₁ -C₄ alkoxy)C₁ -C₄ alkyl, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical;

more preferably, R⁵ and R⁶ are each independently a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical;

more preferably, R⁵ and R⁶ are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ -C₂ alkylamino, di(C₁ -C₂ alkyl)amino, hydroxy, methoxy or ethoxy radical; most preferably, R⁵ and R⁶ are each a hydrogen radical;

R⁷ is a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical;

preferably, R⁷ is a hydrogen, C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, C₁ -C₄ haloalkoxy of 1-3 halo radicals, C₁ -C₄ aminoalkyl, (C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, di(C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, aminosulfonyl, C₁ -C₄ alkylaminosulfonyl, di(C₁ -C₄ alkyl)aminosulfonyl, hydroxy, C₁ -C₄ hydroxyalkyl, thiol, C₁ -C₄ alkylthiol, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, C₁ -C₄ alkoxy, (C₁ -C₄ alkoxy)C₁ -C₄ alkyl, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical;

more preferably, R⁷ is a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical;

more preferably, R⁷ is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; most preferably, R⁷ is a hydrogen radical.

The compounds of this invention may have in general several asymmetric centers and are typically depicted in the form of racemic mixtures. This invention is intended to encompass racemic mixtures, partially racemic mixtures and separate enantiomers and diasteromers.

Compounds of interest include the following:

2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2,4-dimethylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(2,6-dimethyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine;

2-(2-methylphenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methylphenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methylphenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(1-naphthyloxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-(1-naphthyloxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methyl-3-pyridyloxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-((3,5-dimethyl-4-isoxazolyl)carbonylamino)pyridine;

2-(2-methyl-4-chlorophenylthiol)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylthiol)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2,6-dichlorophenylcarbonylamino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2,6-dimethylphenyl carbonylamino)pyridine; and

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine.

As utilized herein, the following terms shall have the following meanings:

"Alkyl", alone or in combination, means a straight-chain or branched-chain alkyl radical containing preferably 1-15 carbon atoms (C₁ -C₁₅), more preferably 1-8 carbon atoms (C₁ -C₈), even more preferably 1-6 carbon atoms (C₁ -C₆), yet more preferably 1-4 carbon atoms (C₁ -C₄), still more preferably 1-3 carbon atoms (C₁ -C₃), and most preferably 1-2 carbon atoms (C₁ -C₂). Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl, octyl and the like.

"Hydroxyalkyl", alone or in combination, means an alkyl radical as defined above wherein at least one hydrogen radical is replaced with a hydroxyl radical, preferably 1-3 hydrogen radicals are replaced by hydroxyl radicals, more preferably 1-2 hydrogen radicals are replaced by hydroxyl radicals, and most preferably one hydrogen radical is replaced by a hydroxyl radical. Examples of such radicals include hydroxymethyl, 1-, 2-hydroxyethyl, 1-, 2-, 3-hydroxypropyl, 1,3-dihydroxy-2-propyl, 1,3-dihydroxybutyl, 1,2,3,4,5,6-hexahydroxy-2-hexyl and the like.

"Alkenyl", alone or in combination, means a straight-chain or branched-chain hydrocarbon radical having one or more double bonds, preferably 1-2 double bonds and more preferably one double bond, and containing preferably 2-15 carbon atoms (C₂ -C₁₅), more preferably 2-8 carbon atoms (C₂ -C₈), even more preferably 2-6 carbon atoms (C₂ -C₆), yet more preferably 2-4 carbon atoms (C₂ -C₄), and still more preferably 2-3 carbon atoms (C₂ -C₃). Examples of such alkenyl radicals include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl and the like.

"Alkoxy", alone or in combination, means a radical of the type "R--O--" wherein "R" is an alkyl radical as defined above and "O" is an oxygen atom. Examples of such alkoxy radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.

"Alkoxycarbonyl", alone or in combination, means a radical of the type "R--O--C(O)--" wherein "R--O--" is an alkoxy radical as defined above and "C(O)" is a carbonyl radical.

"Alkoxycarbonylamino", alone or in combination, means a radical of the type "R--O--C(O)--NH--" wherein "R--O--C(O)" is an alkoxycarbonyl radical as defined above, wherein the amino radical may optionally be substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

"Alkylthio", alone or in combination, means a radical of the type "R--S--" wherein "R" is an alkyl radical as defined above and "S" is a sulfur atom. Examples of such alkylthio radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, iso-butylthio, sec-butylthio, tert-butylthio and the like.

"Alkylsulfinyl", alone or in combination, means a radical of the type "R--S(O)--" wherein "R" is an alkyl radical as defined above and "S(O)" is a mono-oxygenated sulfur atom. Examples of such alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, iso-butylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl and the like.

"Alkylsulfonyl", alone or in combination, means a radical of the type "R--S(O)₂ --" wherein "R" is an alkyl radical as defined above and "S(O)₂ " is a di-oxygenated sulfur atom. Examples of such alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, iso-butylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl and the like.

"Aryl", alone or in combination, means a phenyl or biphenyl radical, which is optionally benzo fused or heterocyclo fused and which is optionally substituted with one or more substituents selected from alkyl, alkoxy, halogen, hydroxy, amino, azido, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, alkanoylamino, amido, amidino, alkoxycarbonylamino, N-alkylamidino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, N-alkylamido, N,N-dialkylamido, aralkoxycarbonylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, oxo and the like. Examples of aryl radicals are phenyl, o-tolyl, 4-methoxyphenyl, 2-(tert-butoxy)phenyl, 3-methyl-4-methoxyphenyl, 2-CF₃ -phenyl, 2-fluorophenyl, 2-chlorophenyl, 3-nitrophenyl, 3-aminophenyl, 3-acetamidophenyl, 2-amino-3-(aminomethyl)phenyl, 6-methyl-3-acetamidophenyl, 6-methyl-2-aminophenyl, 6-methyl-2,3-diaminophenyl, 2-amino-3-methylphenyl, 4,6-dimethyl-2-aminophenyl, 4-hydroxyphenyl, 3-methyl-4-hydroxyphenyl, 4-(2-methoxyphenyl)phenyl, 2-amino-1-naphthyl, 2-naphthyl, 3-amino-2-naphthyl, 1-methyl-3-amino-2-naphthyl, 2,3-diamino-1-naphthyl, 4,8-dimethoxy-2-naphthyl and the like.

"Aralkyl" and "arylalkyl", alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by an aryl radical as defined above, such as benzyl, 1-, 2-phenylethyl, dibenzylmethyl, hydroxyphenylmethyl, methylphenylmethyl, diphenylmethyl, dichlorophenylmethyl, 4-methoxyphenylmethyl and the like.

"Aralkoxy", alone or in combination, means an alkoxy radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by an aryl radical as defined above, such as benzyloxy, 1-, 2-phenylethoxy, dibenzylmethoxy, hydroxyphenylmethoxy, methylphenylmethoxy, dichlorophenylmethoxy, 4-methoxyphenylmethoxy and the like.

"Aralkoxycarbonyl", alone or in combination, means a radical of the type "R--O--C(O)--" wherein "R--O--" is an aralkoxy radical as defined above and "--C(O)--" is a carbonyl radical.

"Alkanoyl", alone or in combination, means a radical of the type "R--C(O)--" wherein "R" is an alkyl radical as defined above and "--C(O)--" is a carbonyl radical. Examples of such alkanoyl radicals include acetyl, trifluoroacetyl, hydroxyacetyl, propionyl, butyryl, valeryl, 4-methylvaleryl, and the like.

"Alkanoylamino", alone or in combination, means a radical of the type "R--C(O)--NH--" wherein "R--C(O)--" is an alkanoyl radical as defined above, wherein the amino radical may optionally be substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

"Aminocarbonyl", alone or in combination, means an amino substituted carbonyl (carbamoyl) radical, wherein the amino radical may optionally be mono- or di-substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkanoyl, alkoxycarbonyl, aralkoxycarbonyl and the like.

"Aminosulfonyl", alone or in combination, means an amino substituted sulfonyl radical.

"Benzo", alone or in combination, means the divalent radical C₆ H₄ =derived from benzene. "Benzo fused" forms a ring system in which benzene and a cycloalkyl or aryl group have two carbons in common, for example tetrahydronaphthylene and the like.

"Bicyclic" as used herein is intended to include both fused ring systems, such as naphthyl and β-carbolinyl, and substituted ring systems, such as biphenyl, phenylpyridyl and diphenylpiperazinyl.

"Cycloalkyl", alone or in combination, means a saturated or partially saturated, preferably one double bond, monocyclic, bicyclic or tricyclic carbocyclic alkyl radical, preferably monocyclic, containing preferably 5-12 carbon atoms (C₅ -C₁₂), more preferably 5-10 carbon atoms (C₅ -C₁₀), even more preferably 5-7 carbon atoms (C₅ -C₇), which is optionally benzo fused or heterocyclo fused and which is optionally substituted as defined herein with respect to the definition of aryl. Examples of such cycloalkyl radicals include cyclopentyl, cyclohexyl, dihydroxycyclohexyl, ethylenedioxycyclohexyl, cycloheptyl, octahydronaphthyl, tetrahydronaphthyl, octahydroquinolinyl, dimethoxytetrahydronaphthyl, 2,3-dihydro-1H-indenyl, azabicyclo[3.2.1]octyl and the like.

"Heteroatoms" means nitrogen, oxygen and sulfur heteroatoms.

"Heterocyclo fused" forms a ring system in which a heterocyclyl or heteroaryl group of 5-6 ring members and a cycloalkyl or aryl group have two carbons in common, for example indole, isoquinoline, tetrahydroquinoline, methylenedioxybenzene and the like.

"Heterocyclyl" means a saturated or partially unsaturated, preferably one double bond, monocyclic or bicyclic, preferably monocyclic, heterocycle radical containing at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1-2, nitrogen, oxygen or sulfur atom ring member and having preferably 3-8 ring members in each ring, more preferably 5-8 ring members in each ring and even more preferably 5-6 ring members in each ring. "Heterocyclyl" is intended to include sulfone and sulfoxide derivatives of sulfur ring members and N-oxides of tertiary nitrogen ring members, and carbocyclic fused, preferably 3-6 ring carbon atoms and more preferably 5-6 ring carbon atoms, and benzo fused ring systems. "Heterocyclyl" radicals may optionally be substituted on at least one, preferably 1-4, more preferably 1-3, even more preferably 1-2, carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo, thioxo, aryl, aralkyl, heteroaryl, heteroaralkyl, amidino, N-alkylamidino, alkoxycarbonylamino, alkylsulfonylamino and the like, and/or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, alkoxycarbonyl, heteroaralkyl, aryl or aralkyl radicals. More preferably, "heterocyclyl", alone or in combination, is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals. Examples of such heterocyclyl radicals include pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiamorpholinyl, 4-benzyl-piperazin-1-yl, pyrimidinyl, tetrahydrofuryl, pyrazolidonyl, pyrazolinyl, pyridazinonyl, pyrrolidonyl, tetrahydrothienyl and its sulfoxide and sulfone derivatives, 2,3-dihydroindolyl, tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydro-1-oxo-isoquinolinyl, 2,3-dihydrobenzofuryl, benzopyranyl, methylenedioxyphenyl, ethylenedioxyphenyl and the like.

"Heteroaryl" means a monocyclic or bicyclic, preferably monocyclic, aromatic heterocycle radical, having at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1-2, nitrogen, oxygen or sulfur atom ring members and having preferably 5-6 ring members in each ring, which is optionally saturated carbocyclic fused, preferably 3-4 carbon atoms (C₃ -C₄) to form 5-6 ring membered rings and which is optionally substituted as defined above with respect to the definitions of aryl. Examples of such heteroaryl groups include imidazolyl, 1-benzyloxycarbonylimidazol-4-yl, pyrrolyl, pyrazolyl, pyridyl, 3-(2-methyl)pyridyl, 3-(4-trifluoromethyl)pyridyl, pyrimidinyl, 5-(4-trifluoromethyl)pyrimidinyl, pyrazinyl, triazolyl, furyl, thienyl, oxazolyl, thiazolyl, indolyl, quinolinyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolinyl, quinoxalinyl, benzothiazolyl, benzofuryl, benzimidazolyl, benzoxazolyl and the like.

"Heteroaralkyl" and "heteroarylalkyl," alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by a heteroaryl radical as defined above, such as 3-furylpropyl, 2-pyrrolyl propyl, chloroquinolinylmethyl, 2-thienylethyl, pyridylmethyl, 1-imidazolylethyl and the like.

"Halogen" and "halo", alone or in combination, means fluoro, chloro, bromo or iodo radicals.

"Haloalkyl", alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-3, is replaced by a halogen radical, more preferably fluoro or chloro radicals. Examples of such haloalkyl radicals include 1,1,1-trifluoroethyl, chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, bis(trifluoromethyl)methyl and the like.

"Pharmacologically acceptable salt" means a salt prepared by conventional means, and are well known by those skilled in the art. The "pharmacologically acceptable salts" include basic salts of inorganic and organic acids, including but not limited to hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulfonic acid, malic acid, acetic acid, oxalic acid, tartaric acid, citric acid, lactic acid, fumaric acid, succinic acid, maleic acid, salicylic acid, benzoic acid, phenylacetic acid, mandelic acid and the like. When compounds of the invention include an acidic function such as a carboxy group, then suitable pharmaceutically acceptable cation pairs for the carboxy group are well known to those skilled in the art and include alkaline, alkaline earth, ammonium, quaternary ammonium cations and the like. For additional examples of "pharmacologically acceptable salts," see infra and Berge et al, J. Pharm. Sci. 66, 1 (1977).

"Cytokine" means a secreted protein that affects the functions of other cells, particularly as it relates to the modulation of interactions between cells of the immune system or cells involved in the inflammatory response. Examples of cytokines include but are not limited to interleukin 1 (IL-1), preferably IL-1β, interleukin 6 (IL-6), interleukin 8 (IL-8) and TNF, preferably TNF-α (tumor necrosis factor-α).

"TNF, IL-1, IL-6, and/or IL-8 mediated disease or disease state" means all disease states wherein TNF, IL-1, IL-6, and/or IL-8 plays a role, either directly as TNF, IL-1, IL-6, and/or IL-8 itself, or by TNF, IL-1, IL-6, and/or IL-8 inducing another cytokine to be released. For example, a disease state in which IL-1 plays a major role, but in which the production of or action of IL-1 is a result of TNF, would be considered mediated by TNF.

"Leaving group" generally refers to groups readily displaceable by a nucleophile, such as an amine, a thiol or an alcohol nucleophile. Such leaving groups are well known in the art. Examples of such leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halides, triflates, tosylates and the like. Preferred leaving groups are indicated herein where appropriate.

"Protecting group" generally refers to groups well known in the art which are used to prevent selected reactive groups, such as carboxy, amino, hydroxy, mercapto and the like, from undergoing undesired reactions, such as nucleophilic, electrophilic, oxidation, reduction and the like. Preferred protecting groups are indicated herein where appropriate. Examples of amino protecting groups include, but are not limited to, aralkyl, substituted aralkyl, cycloalkenylalkyl and substituted cycloalkenyl alkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl, silyl and the like. Examples of aralkyl include, but are not limited to, benzyl, ortho-methylbenzyl, trityl and benzhydryl, which can be optionally substituted with halogen, alkyl, alkoxy, hydroxy, nitro, acylamino, acyl and the like, and salts, such as phosphonium and ammonium salts. Examples of aryl groups include phenyl, naphthyl, indanyl, anthracenyl, 9-(9-phenylfluorenyl), phenanthrenyl, durenyl and the like. Examples of cycloalkenylalkyl or substituted cycloalkylenylalkyl radicals, preferably have 6-10 carbon atoms, include, but are not limited to, cyclohexenyl methyl and the like. Suitable acyl, alkoxycarbonyl and aralkoxycarbonyl groups include benzyloxycarbonyl, t-butoxycarbonyl, iso-butoxycarbonyl, benzoyl, substituted benzoyl, butyryl, acetyl, tri-fluoroacetyl, tri-chloro acetyl, phthaloyl and the like. A mixture of protecting groups can be used to protect the same amino group, such as a primary amino group can be protected by both an aralkyl group and an aralkoxycarbonyl group. Amino protecting groups can also form a heterocyclic ring with the nitrogen to which they are attached, for example, 1,2-bis(methylene)benzene, phthalimidyl, succinimidyl, maleimidyl and the like and where these heterocyclic groups can further include adjoining aryl and cycloalkyl rings. In addition, the heterocyclic groups can be mono-, di- or tri-substituted, such as nitrophthalimidyl. Amino groups may also be protected against undesired reactions, such as oxidation, through the formation of an addition salt, such as hydrochloride, toluenesulfonic acid, trifluoroacetic acid and the like. Many of the amino protecting groups are also suitable for protecting carboxy, hydroxy and mercapto groups. For example, aralkyl groups. Alkyl groups are also suitable groups for protecting hydroxy and mercapto groups, such as tert-butyl.

Silyl protecting groups are silicon atoms optionally substituted by one or more alkyl, aryl and aralkyl groups. Suitable silyl protecting groups include, but are not limited to, trimethylsilyl, triethylsilyl, tri-isopropylsilyl, tert-butyldimethylsilyl, dimethylphenylsilyl, 1,2-bis(dimethylsilyl)benzene, 1,2-bis(dimethylsilyl)ethane and diphenylmethylsilyl. Silylation of an amino groups provide mono- or di-silylamino groups. Silylation of aminoalcohol compounds can lead to a N,N,O-tri-silyl derivative. Removal of the silyl function from a silyl ether function is readily accomplished by treatment with, for example, a metal hydroxide or ammonium flouride reagent, either as a discrete reaction step or in situ during a reaction with the alcohol group. Suitable silylating agents are, for example, trimethylsilyl chloride, tert-butyl-dimethylsilyl chloride, phenyldimethylsilyl chloride, diphenylmethyl silyl chloride or their combination products with imidazole or DMF. Methods for silylation of amines and removal of silyl protecting groups are well known to those skilled in the art. Methods of preparation of these amine derivatives from corresponding amino acids, amino acid amides or amino acid esters are also well known to those skilled in the art of organic chemistry including amino acid/amino acid ester or aminoalcohol chemistry.

Protecting groups are removed under conditions which will not affect the remaining portion of the molecule. These methods are well known in the art and include acid hydrolysis, hydrogenolysis and the like. A preferred method involves removal of a protecting group, such as removal of a benzyloxycarbonyl group by hydrogenolysis utilizing palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. A t-butoxycarbonyl protecting group can be removed utilizing an inorganic or organic acid, such as HCl or trifluoroacetic acid, in a suitable solvent system, such as dioxane or methylene chloride. The resulting amino salt can readily be neutralized to yield the free amine. Carboxy protecting group, such as methyl, ethyl, benzyl, tert-butyl, 4-methoxyphenylmethyl and the like, can be removed under hydrolysis and hydrogenolysis conditions well known to those skilled in the art.

The symbols used above have the following meanings: ##STR5##

Procedures for preparing the compounds of this invention are set forth below. It should be noted that the general procedures are shown as it relates to preparation of compounds having unspecified stereochemistry. However, such procedures are generally applicable to those compounds of a specific stereochemistry, e.g., where the stereochemistry about a group is (S) or (R). In addition, the compounds having one stereochemistry (e.g., (R)) can often be utilized to produce those having opposite stereochemistry (i.e., (S)) using well-known methods, for example, by inversion.

Preparation of Compounds of Formula I

The compounds of the present invention represented by Formula I above can be prepared utilizing the following general procedures. Hetero-aromatic Nitrogen Compounds; Pyrroles and Pyridines: Schofield, Kenneth; Plenum Press, New York, N.Y.; (1967) and Advances in Nitrogen Heterocycles: JAI Press, Greenwich, Conn.; (1995) describe procedures and references that may be useful in preparing compounds of the present invention.

2-Halo-5-nitro-pyridine analogs (2) can be treated with the appropriate amine, alcohol, phenol, or thiol (R¹ --X--H) in the presence of base or Cu(I) in an appropriate solvent, such as THF, DMF, DME, DMSO and the like, at a temperature from -20° C. to 120° C. to form 2-substituted-5-nitropyridines (3) (Scheme I). Reduction of the nitro group can be perfomed by treatment of (3) with hydrogen gas in the presence of palladium on carbon or Raney nickel, or alternatively, by treatment with SnCl₂ in an alcoholic solvent and in the presence or absence of HCl to obtain 2-substituted-5-aminopyridines (4). The aminopyridines (4) may be alkylated using alkylhalides and an appropriate base or by reductive alkylation employing the appropriate aldehyde or ketone in the presence of a reducing agent, such as sodium triacetoxy borohydride, borane THF and the like, to form the substituted aminopyridines (5). Either (4) or (5) may be acylated with an appropriate acid halide (e.g., R³ C(O)Cl or R³ C(O)Br) in the presence of a base, such as pyridine, DMAP and the like, or alternatively may be acylated with an anhydride, either mixed or symmetrical, or alternatively may be acylated by treatment with the appropriate acid (R³ CO₂ H) in the presence of a coupling agent such as a carbodiimide reagent to form the final product (1). Alternatively, substituted 2-bromo-5-nitropyridine analogs may be reduced to, substituted 2-bromo-5-aminopyridine analogs by the action of SnBr₂ in methanolic solvent. Subsequent acylation with an appropriate activated ester (i.e.: R³ CO₂ H in the presence of diisopropylcarbodiimide in methylene chloride as solvent) produces 2-bromopyridine-5-carboxamide compounds of structure (5a). Coupling of (5a) with an appropriate phenol in the presence of Cu(Ac)₂ and K₂ CO₃ in DMF at 140° C. provides compounds of formula (1) where X=O. ##STR6##

6-Substituted-2-halo-5-nitro-pyridine analogs (6) may be prepared from 2,6-dichloro-5-nitropyridine according to the methods outlined in Scheme II. Treatment with one equivalent of an appropriate nucleophile of R⁷ or a precursor thereof (such as, HO⁻⁻, RO⁻⁻, AcS⁻⁻, NC⁻⁻, RS⁻⁻ and the like) provides (6). Subsequent reaction to form (7) (treatment with R¹ --X--H in the presence of base or Cu(I) in an appropriate solvent, such as THF, DMF, DME, DMSO and the like, at a temperature from -20° C. to 120° C.) and (8) (reduction of the nitro group and substitution with R⁴) is as described in Scheme I (cf. Colbry, N. L. et al.; J. Heterocyclic Chem., 21: 1521-1525 (1984); Matsumoto, Jun-ichi, et al.; J. Heterocyclic Chem., 21: 673-679 (1984)). (8) may be reacted with an acid halide or an activated ##STR7## ester as shown in Scheme I to provide compounds of formula (1). Where R⁷ =CN, compounds of formula (8) may be hydrolyzed to acids (R⁷ =CO₂ H) of formula (9) using acidic media such as HBr and the like. Utilizing the appropriate N-protecting groups, acids of formula (9) may be transformed into esters, amides and alcohols. Compounds of formula (9) and derivatives described above may be be reacted with an acid halide or an activated ester as shown in Scheme I to provide compounds of formula (1). Compounds of formula (8), where R⁷ =--CN, may be reduced to the primary amine (R⁷ =--CH₂ NH₂) using reagents such as BH₃ or hydrogen gas in the presence of palladium on carbon or Raney nickel. Subsequent manipulation and reaction of the primary amine may be performed in the presence of the pyridine-5-amine substituent due to it's greater reactivity. Specifically, compounds of formula (8) where R⁷ =--CH₂ NH₂ may be alkylated by treatment with an appropriate aldehyde or ketone in the presence of a reducing agent, such as sodium triacetoxy borohydride, or may be acylated by treatment with an appropriate activated ester, chloroformate, isocyanate and the like, or may be sulfonylated by treatment with an appropriate sulfonyl halide. Alternatively, substituted 3-aminopyridine intermediates may be prepared from the corresponding nicotinamide compound using Hofmann's reaction.

When R⁶ and/or R⁷ is an alkyl group, such as methyl, in compound (7), containing the appropriate protecting groups of or avoiding the presence of base sensitive groups, can be treated with strong base such as NaNH₂, PhLi, NaH or the like at temperatures from -78° C. to 22° C. then treated with electrophiles, such as alkyl halides, aldehydes, ketones and the like (cf. Fuerst, Feustel; CHEMTECH; 10: 693-699 (1958); Nishigaki, S. et al.; Chem. Pharm. Bull.; 17: 1827-1831 (1969); Kaiser, Edwin M.; Tetrahedron; 39: 2055-2064 (1983)). Alternatively, the alkyl group may be halogenated and the haloalkyl group may be reacted with a nucleophile, such as an amino group, alkoxy, alkylthiol and the like.

6-Chloronicotinoyl chloride analogs (10) are treated with the appropriate amine (R³ R⁴ NH) in the presence of base in an appropriate solvent, such as dichloromethane, acetonitrile, DMF, THF and the like, at a temperature from -20° C. to 120° C. to form nicotinamides (11) as shown in Scheme III. Alternatively, 6-chloronicotinic acid analogs (12) may be coupled with the appropriate amine via an anhydride, either mixed or symmetrical, or alternatively by treatment with the appropriate amine in the presence of a coupling agent such as a carbodiimide reagent to form the amide (11). 6-Chloronicotinamide analogs (11) are treated with the appropriate R¹ --X--H in the presence of absence of base, or Cu(I) in an appropriate solvent, such as pyridine, ethylene glycol, DMF, DME, DMSO and the like, at a temperature from -20° C. to 180° C. to form the final product (13). ##STR8##

Substituted halopyridines may be readily prepared from the corresponding pyridones using phosphorus oxychloride or pentachloride.

Amines of formula NHR¹ R² and NHR³ R⁴ are commercially available or can be readily prepared by those skilled in the art from commercially available starting materials. For example, an amide, nitro or cyano group can be reduced under reducing conditions, such as in the prescence of a reducing agent like lithium aluminum hydride and the like, to form the corresponding amine. Alkylation and acylation of amino groups are well known in the art. Chiral and achiral substituted amines can be prepared from chiral amino acids and amino acid amides (for example, alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and the like) using methods well known in the art, such as H. Brunner, P. Hankofer, U. Holzinger, B. Treittinger and H. Schoenenberger, Eur. J. Med. Chem. 25, 35-44, 1990; M. Freifelder and R. B. Hasbrouck, J. Am. Chem. Soc. 82, 696-698, 1960; Dornow and Fust, Chem. Ber. 87, 985, 1954; M. Kojima and J. Fujita, Bull. Chem. Soc. Jpn. 55, 1454-1459, 1982; W. Wheeler and D. O'Bannon, Journal of Labelled Compounds and Radiopharmaceuticals XXXI, 306, 1992; and S. Davies, N. Garrido, O. Ichihara and I. Walters, J. Chem. Soc., Chem. Commun. 1153, 1993.

Alkyl sulfonic acids, aryl sulfonic acids, heterocyclyl sulfonic acids, heteroaryl sulfonic acids, alkylmercaptans, arylmercaptans, heterocyclylmercaptans, heteroarylmercaptans, alkylhalides, arylhalides, heterocyclylhalides, heteroarylhalides, and the like are commercially available or can be readily prepared from starting materials commercially available using standard methods well known in the art.

Thioether derivatives can be converted into the corresponding sulfone or sulfoxide by oxidizing the thioether derivative with a suitable oxidation agent in a suitable solvent. Suitable oxidation agents include, for example, hydrogen peroxide, sodium meta-perborate, oxone (potassium peroxy monosulfate), meta-chloroperoxybenzoic acid, periodic acid and the like, including mixtures thereof. Suitable solvents include acetic acid (for sodium meta-perborate) and, for other peracids, ethers such as THF and dioxane, and acetonitrile, DMF and the like, including mixtures thereof.

The chemical reactions described above are generally disclosed in terms of their broadest application to the preparation of the compounds of this invention. Occasionally, the reactions may not be applicable as described to each compound included within the disclosed scope. The compounds for which this occurs will be readily recognized by those skilled in the art. In all such cases, either the reactions can be successfully performed by conventional modifications known to those skilled in the art, e.g., by appropriate protection of interfering groups, by changing to alternative conventional reagents, by routine modification of reaction conditions, and the like, or other reactions disclosed herein or otherwise conventional, will be applicable to the preparation of the corresponding compounds of this invention. In all preparative methods, all starting materials are known or readily prepared from known starting materials.

Prodrugs of the compounds of this invention are also contemplated by this invention. A prodrug is an active or inactive compound that is modified chemically through in vivo physicological action, such as hydrolysis, metabolism and the like, into a compound of this invention following adminstration of the prodrug to a patient. The suitability and techniques involved in making and using prodrugs are well known by those skilled in the art. For a general discussion of prodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews 165 (1988) and Bundgaard Design of Prodrugs, Elsevier (1985). Examples of a masked carboxylate anion include a variety of esters, such as alkyl (for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl (for example, benzyl, p-methoxybenzyl), and alkylcarbonyloxyalkyl (for example, pivaloyloxymethyl). Amines have been masked as arylcarbonyloxymethyl substituted derivatives which are cleaved by esterases in vivo releasing the free drug and formaldehyde (Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group, such as imidazole, imide, indole and the like, have been masked with N-acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)). Hydroxy groups have been masked as esters and ethers. EP 039,051 (Sloan and Little, Apr. 11, 1981) discloses Mannich-base hydroxamic acid prodrugs, their preparation and use.

Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. The following Examples illustrate the preparation of compounds of the present invention and intermediates useful in preparing the compounds of the present invention.

EXAMPLE 1 ##STR9## Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine

Step A: 2-(4-Chloro-2-methyl-phenoxy)-5-nitropyridine

4-Chloro-2-methylphenol (101 mg, 0.71 mmol) was dissolved in tetrahydrofuran (2.1 mL) and the solution was treated with sodium hydride (60% dispersed in mineral oil, 31 mg, 0.78 mmol). After stirring for 30 minutes at 22° C., 2-chloro-5-nitropyridine (101 mg, 0.64 mmol) was added and the reaction mixture was heated to reflux for 1 hour. The solution was cooled to ambient temperature, quenched with saturated aqueous NH₄ Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2× with saturated NaHCO₃, saturated NaCl, dried over anhydrous Na₂ SO₄ and concentrated in vacuo.

Step B: 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine

2-(4-chloro-2-methyl-phenoxy)-5-nitropyridine (203 mg, 0.77 mmol) was dissolved in 95% ethanol (3 mL) and treated with 20% palladium hydroxide on carbon (50 mg). The reaction mixture was shaken in a hydrogen atmosphere (40 psi) for 1 hour. The solution was filtered through celite and concentrated in vacuo. MS (m/z): 234/236 (M+H)⁺ ; C₁₂ H₁₁ N₂ OCl requires 234.7.

EXAMPLE 2

The compounds listed in Table 1 were prepared from 2-chloro-5-nitropyridine and the appropriate alcohol, amine or thiol in the same manner as 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine was prepared.

                  TABLE 1                                                          ______________________________________                                                                MS                                                                             (m/z)                                                   ______________________________________                                         2-(4-Chloro-2-methylphenoxy)-5-amino-pyridine                                                           235                                                   2-(4-Chloro-2,6-dimethylphenoxy)-5-amino-                                                               249                                                   pyridine                                                                       2-(2-Methyl-pyridin-3-yloxy)-5-amino-pyridine                                                           201                                                   2-(4-Fluoro-2-methylphenoxy)-5-amino-pyridine                                                           218                                                   2-(2-Isopropylphenoxy)-5-amino-pyridine                                                                 228                                                   2-(1-Naphthyloxy)-5-amino-pyridine                                                                      236                                                   2-(Cyclohexyloxy)-5-amino-pyridine                                                                      192                                                   2-(2-Methylphenoxy)-5-amino-pyridine                                                                    200                                                   2-(2,4-Dimethylphenoxy)-5-amino-pyridine                                                                214                                                   2-(4-Chlorophenoxy)-5-amino-pyridine                                                                    222                                                   2-(Phenoxy)-5-amino-pyridine                                                                            186                                                   2-(2-Methylcyclohexylamino)-5-amino-pyridine                                                            205                                                   2-(Cyclohexylamino)-5-amino-pyridine                                                                    191                                                   2-(2-Methylanilino)-5-amino-pyridine                                                                    199                                                   2-(4-Chloro-2-methylanilino)-5-amino-pyridine                                                           233                                                   2-(2,4-Dimethylanilino)-5-amino-pyridine                                                                212                                                   2-(4-Chloro-2-methylthiophenoxy)-5-amino-                                                               251                                                   pyridine                                                                       ______________________________________                                    

EXAMPLE 3 ##STR10## Preparation of 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine

Step A: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-nitropyridine

Sodium hydride (60% in mineral oil, 1.08 g, 27 mmol) was washed 3× with hexanes then a solution of 4-chloro-2-methylphenol (3.50 g, 24.5 mmol) dissolved in tetrahydrofuran (40 mL) was added. The solution was stirred for 20 minutes then 2-chloro-3-methyl-5-nitropyridine (4.02 g, 23.3 mmol) was added and the reaction mixture was heated to reflux for 3 hours. After cooling, the mixture was concentrated in vacuo then dissolved in ethyl acetate and washed with water, 3× with saturated NaHCO₃ and saturated NaCl then dried over Na₂ SO₄ and concentrated in vacuo.

Step B: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine

2- (4-chloro-2-methyl-phenoxy) -3-methyl-5-nitropyridine (5.8 g, 20.8 mmol) was dissolved in 95% ethanol (50 mL) and treated with 20% palladium hydroxide on carbon (350 mg). The reaction mixture was shaken in a hydrogen atmosphere (40 psi) for 1 hour. The solution was filtered through celite and concentrated in vacuo followed by chromatography on SiO₂ using 1:1 ethyl acetate/hexanes as eluant. MS (m/z): 248/250 (M+H)⁺ ; C₁₃ H₁₃ N₂ OCl requires 248.7.

EXAMPLE 4

The compounds listed in Table 2 were prepared from substituted 2-chloro-5-nitropyridine and 4-chloro-2-methylphenol in the same manner as 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine was prepared.

                  TABLE 2                                                          ______________________________________                                                                 MS                                                                             (m/z)                                                  ______________________________________                                         2-(4-Chloro-2-methyl-phenoxy)-4-methyl-5-amino-                                                          249                                                  pyridine                                                                       6-(4-Chloro-2-methyl-phenoxy)-2-methyl-3-amino-                                                          249                                                  pyridine                                                                       6-(4-Chloro-2-methyl-phenoxy)-2,3-diamino-                                                               250                                                  pyridine                                                                       ______________________________________                                    

EXAMPLE 5 ##STR11## Preparation of N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide

2-(4-Chloro-2-methyl-phenoxy)-5-aminopyridine (211 mg, 0.90 mmol) was dissolved in methylene chloride (2.7 mL) then treated with triethylamine (0.19 mL, 1.35 mmol) followed by benzoyl chloride (0.13 mL, 1.12 mmol). The reaction mixture was stirred for 3 hours at 22° C. then saturated aqueous NaHCO₃ was added and the mixture was stirred for another hour. The organic layer was separated and washed 2× with 6% aqueous NaHCO₃, dried over Na₂ SO₄ and concentrated in vacuo. The residue was chromatographed on silica gel using 1:1 ethyl acetate/hexane as eluent. The product was recovered as a white solid. MS (m/z): 338/340 (M+H)⁺ ; C₁₉ H₁₅ N₂ O₂ Cl requires 338.8.

EXAMPLE 6

The compounds listed in Table 3 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide was prepared.

                  TABLE 3                                                          ______________________________________                                                                 MS                                                                             (m/z)                                                  ______________________________________                                         2-(4-Chloro-2-methyl-phenoxy)-5-(3-                                                                      340                                                  pyridylcarbonylamino)pyridine                                                  2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   408                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-Chloro-2-methyl-phenoxy)-5-(4-                                                                      340                                                  pyridylcarbonylamino)pyridine                                                  2-(4-Chloro-2-methyl-phenoxy)-5-((4-                                                                     369                                                  methoxyphenyl)carbonylamino)pyridine                                           2-(4-Chloro-2-methyl-phenoxy)-5-((4-                                                                     409                                                  pentylphenyl)carbonylamino)pyridine                                            2-(4-Chloro-2-methyl-phenoxy)-5-(2-                                                                      389                                                  naphthylcarbonylamino)pyridine                                                 2-(4-Chloro-2-methyl-phenoxy)-5-(2-                                                                      345                                                  thienylcarbonylamino)pyridine                                                  2-(4-Chloro-2-methyl-phenoxy)-5-((3,5-dimethyl-                                                          358                                                  4-isoxazolyl) carbonylamino) pyridine                                          2-(4-Chloro-2-methyl-phenoxy)-5-((5-                                                                     383                                                  benzo[1,3]dioxol-yl)carbonylamino)pyridine                                     2-(4-Chloro-2-methyl-phenoxy)-5-((5-tert-butyl-                                                          399                                                  2-methyl-2H-pyrazol-3-yl)carbonylamino)pyridine                                2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     395                                                  benzo[b]thiophenyl)carbonylamino)pyridine                                      2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     369                                                  methoxyphenyl)carbonylamino)pyridine                                           2-(4-Chloro-2-methyl-phenoxy)-5-((3,5-                                                                   408                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   367                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     353                                                  methylphenyl)carbonylamino)pyridine                                            2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     384                                                  nitrophenyl)carbonylamino)pyridine                                             2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     397                                                  acetoxyphenyl)carbonylamino)pyridine                                           2-(4-chloro-2,6-dimethylphenoxy)-5-((2,6-                                                                422                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-chloro-2,6-dimethylphenoxy)-5-((2,6-                                                                381                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2-methyl-pyridin-3-yloxy)-5-((2,6-                                                                    374                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2-methyl-pyridin-3-yloxy)-5-((2,6-                                                                    333                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2-methyl-pyridin-3-yloxy)-5-((2-                                                                      319                                                  methylphenyl)carbonylamino)pyridine                                            2-(4-fluoro-2-methylphenoxy)-5-((2,6-                                                                    391                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-fluoro-2-methylphenoxy)-5-((2,6-                                                                    350                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(4-fluoro-2-methylphenoxy)-5-((2-                                                                      336                                                  methylphenyl)carbonylamino)pyridine                                            2-(4-fluoro-2-methylphenoxy)-5-((2-                                                                      390                                                  trifluoromethylphenyl)carbonylamino)pyridine                                   2-(4-fluoro-2-methylphenoxy)-5-((2-                                                                      340                                                  fluorophenyl)carbonylamino)pyridine                                            2-(2-isopropylphenoxy)-5-((2,6-                                                                          401                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2-isopropylphenoxy)-5-((2,6-                                                                          360                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2-isopropylphenoxy)-5-((2-                                                                            346                                                  methylphenyl)carbonylamino)pyridine                                            2-(1-naphthyloxy)-5-((2,6-                                                                               409                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(1-naphthyloxy)-5-((2,6-                                                                               368                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(1-naphthyloxy)-5-((2-  354                                                  methylphenyl)carbonylamino)pyridine                                            2-(cyclohexyloxy)-5-((2,6-                                                                               365                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(cyclohexyloxy)-5-((2,6-                                                                               324                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(cyclohexyloxy)-5-((2-  331                                                  chlorophenyl)carbonylamino)pyridine                                            2-(cyclohexyloxy)-5-((2-  310                                                  methylphenyl)carbonylamino)pyridine                                            2-(2-methylphenoxy)-5-((2,6-                                                                             373                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2-methylphenoxy)-5-((2,6-                                                                             332                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2-methylphehoxy)-5-((2-                                                                               339                                                  chlorophenyl)carbonylamino)pyridine                                            2-(2-methylphenoxy)-5-((2-                                                                               318                                                  methylphenyl)carbonylamino)pyridine                                            2-(2,4-dimethylphenoxy)-5-((2,6-                                                                         387                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2,4-dimethylphenoxy)-5-((2,6-                                                                         346                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2,4-dimethylphenoxy)-5-((2-                                                                           353                                                  chlorophenyl)carbonylamino)pyridine                                            2-(2,4-dimethylphenoxy)-5-((2-                                                                           332                                                  methylphenyl)carbonylamino)pyridine                                            2-(4-chlorophenoxy)-5-((2,6-                                                                             394                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-chlorophenoxy)-5-((2,6-                                                                             353                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2-methylcyclohexylamino)-5-((2,6-                                                                     378                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2-methylcyclohexylamino)-5-((2-                                                                       323                                                  methylphenyl)carbonylamino)pyridine                                            2-(cyclohexylamino)-5-((2,6-                                                                             364                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(cyclohexylamino)-5-((2,6-                                                                             323                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(cyclohexylamino)-5-((2-                                                                               309                                                  methylphenyl)carbonylamino)pyridine                                            2-(2-methylamino)-5-((2,6-                                                                               372                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2-methylamino)-5-((2,6-                                                                               331                                                  dimethylphenyl) carbonylamino) pyridine                                        2-(2-methylanilino)-5-((2-                                                                               317                                                  methylphenyl)carbonylamino)pyridine                                            2-(4-chloro-2-methylanilino)-5-((2,6-                                                                    407                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-chloro-2-methylanilino)-5-((2,6-                                                                    366                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(4-chloro-2-methylanilino)-5-((2-                                                                      352                                                  methylphenyl)carbonylamino)pyridine                                            2-(2,4-dimethylanilino)-5-((2,6-                                                                         386                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(2,4-dimethylanilino)-5-((2,6-                                                                         345                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(2,4-dimethylamino)-5-((2-                                                                             331                                                  methylphenyl)carbonylamino)pyridine                                            2-(2,4-dimethylamino)-5-((2-                                                                             352                                                  chlorophenyl)carbonylamino)pyridine                                            2-(2,4-dimethylanilino)-5-((2-                                                                           335                                                  fluorophenyl)carbonylamino)pyridine                                            2-(4-chloro-2-methyl-thiophenyl)-5-((2,6-                                                                424                                                  dichlorophenyl)carbonylamino)pyridine                                          2-(4-chloro-2-methyl-thiophenyl)-5-((2,6-                                                                383                                                  dimethylphenyl)carbonylamino)pyridine                                          2-(4-chloro-2-methyl-thiophenyl)-5-((2-                                                                  369                                                  methylphenyl)carbonylamino)pyridine                                            ______________________________________                                    

EXAMPLE 7

The compounds listed in Table 4 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide was prepared.

                  TABLE 4                                                          ______________________________________                                                                 MS                                                                             (m/z)                                                  ______________________________________                                         2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   422                                                  dichlprophenyl)carbonylamino)-3-methyl-pyridine                                2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     387                                                  chlorophenyl)carbonylamino)-3-methyl-pyridine                                  2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     367                                                  methylphenyl)carbonylamino)-3-methyl-pyridine                                  2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   332                                                  dimethylphenyl)carbonylamino)-3-methyl-pyridine                                2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   422                                                  dichlorophenyl)carbonylamino)-4-methyl-pyridine                                2-(4-Chloro-2-methyl-phenoxy)-5-((2-fluoro-6-                                                            439                                                  trifluoromethylphenyl)carbonylamino)-4-methyl-                                 pyridine                                                                       2-(4-Chloro-2-methyl-phenoxy)-5-((2,4,6-                                                                 479                                                  triisopropylphenyl)carbonylamino)-4-methyl-                                    pyridine                                                                       2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     367                                                  methylphenyl)carbonylamino)-6-methyl-pyridine                                  2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     387                                                  chlorophenyl)carbonylamino)-6-methyl-pyridine                                  2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   422                                                  dichlorophenyl)carbonylamino)-6-methyl-pyridine                                2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   423                                                  dichlorophenyl)carbonylamino)-6-amino-pyridine                                 2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     388                                                  chlorophenyl)carbonylamino)-6-amino-pyridine                                   2-(4-Chloro-2-methyl-phenoxy)-5-((2,6-                                                                   382                                                  dimethylphenyl)carbonylamino)-6-amino-pyridine                                 2-(4-Chloro-2-methyl-phenoxy)-5-((2-                                                                     368                                                  methylphenyl)carbonylamino)-6-amino-pyridine                                   ______________________________________                                    

EXAMPLE 8 ##STR12## Preparation of 2-Amino-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-benzamide

N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-nitro-benzamide (301 mg, 0.7 mmol) was dissolved in 95% ethanol (4 mL) and treated with 20% palladium hydroxide on carbon (Pearlman's catalyst, 50 mg) and subjected to a hydrogen atmosphere (40 psi) for 2 hours. The catalyst was removed by filtration and the solvents were removed in vacuo. The product was purified by chromatography on SiO2 using 1:1 ethyl acetate/hexanes as eluent. MS (m/z) 353/355 (M+H)⁺ ; C₁₉ H₁₆ N₃ O₂ Cl requires 353.8.

EXAMPLE 9 ##STR13## Preparation of N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-hydroxy-benzamide

Acetic acid 2-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-ylcarbamoyl)-phenyl ester (304 mg, 0.77 mmol) dissolved in tetrahydrofuran (3.8 mL) was treated with an aqueous lithium hydroxide solution (1.0 M, 3.8 mL, 3.8 mmol). The solution was stirred for 30 minutes at 22° C. then quenched with aqueous saturated NH₄ Cl. The mixture was diluted with ethyl acetate then the organics were washed with water, 2× saturated NaHCO₃, saturated NaCl, dried over Na₂ SO₄ and concentrated in vacuo. MS (m/z): 354/356 (M+H)⁺ ; C₁₉ H₁₅ N₂ O₃ Cl requires 354.8.

EXAMPLE 10 ##STR14## Preparation of 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine

Step A: 2-(Cyclohexylamino)-5-nitro-pyridine

Sodium hydride (60% dispersion in mineral oil, 1.99 g, 49.8 mmol) was washed 3× with hexanes then a solution of cyclohexylamine (3.8 mL, 33.2 mmol) dissolved in tetrahydrofuran (50 mL) was added. After stirring for 30 minutes at 22° C., 2-chloro-5-nitropyridine (5.00 g, 31.5 mmol) was added and the reaction mixture was heated to reflux for 3 hours. The solution was cooled to ambient temperature, quenched with saturated aqueous NH₄ Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2× with saturated NaHCO₃, saturated NaCl, dried over anhydrous Na₂ SO₄ and concentrated in vacuo. The product was recovered as a brown oil.

Step B: 2-(N-Cyclohexyl-N-methylamino)-5-nitro-pyridine

Sodium hydride (60% dispersion in mineral oil, 0.38 g, 9.48 mmol) was washed 3× with hexanes then a solution of 2-cyclohexylamino-5-nitropyridine (1.88 g, 8.5 mmol) dissolved in dimethylformamide (20 mL) was added. After stirring for 30 minutes at 22° C., the reaction mixture was cooled to 0° C. and methyl iodide (0.55 mL, 8.9 mmol) was added. The solution was stirred for 1.5 hours at 0° C. followed by quenching with saturated aqueous NH₄ Cl. The reaction mixture was diluted with ethyl acetate and extracted 5× with water (200 mL), saturated NaCl, dried over Na₂ SO₄ and concentrated in vacuo oil was chromatographed on SiO₂ using 2:1 hexanes/ethyl acetate as eluent.

Step C: 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine

Cyclohexyl-methyl-(5-nitro-pyridin-2-yl)-amine (1.72 g, 7.3 mmol) was dissolved in ethanol (80 mL) and treated with 20% palladium hydroxide on carbon (Pearlman's catalyst, 0.5 g) and the mixture was shaken under a hydrogen atmosphere (50 psi) for 6 hours. The catalyst was removed by filtration through celite then the filtrate was concentrated in vacuo and the resultant oil was chromatographed on SiO₂ using 1:1 ethyl acetate/hexanes as eluent. MS (m/z): 206 (M+H)⁺ ; C₁₂ H₁₉ N₃ requires 205.3.

EXAMPLE 11 ##STR15## Preparation of 2-(N-(2,4-dimethylphenyl)-N-methylamino)-5-amino-pyridine

2-(N-(2,4-dimethylphenyl)-N-methylamino)-5-amino-pyridine was prepared from 1-amino-2,4-dimethylbenzene and 2-chloro-5-nitropyridine in the same manner as 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine was prepared.

EXAMPLE 12 ##STR16## Preparation of 2,6-Dichloro-N-(2-(N'-cyclohexyl-N'-methylamino)-pyridin-5-yl)-benzamide

2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine (26 mg, 0.13 mmol) dissolved in methylene chloride (0.25 mL) was treated with triethylamine (0.026 mL, 0.18 mmol) followed by a solution of 2,6-dichlorobenzoyl chloride (31 mg, 0.15 mmol) dissolved in methylene chloride (0.15 mL). The reaction mixture was shaken at 22° C. for 18 hours followed by quenching with saturated aqueous NH₄ Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na₂ SO₄ then concentrated in vacuo. The crude product was purified by chromatography on SiO₂ using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 378/380 (M+H)⁺ ; C₁₉ H₂₁ N₃ OCl requires 377.

EXAMPLE 13

The compounds listed in Table 5 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as 2,6-Dichloro-N-(2-(N'-cyclohexyl-N'-methylamino)-pyridin-5-yl)-benzamide was prepared.

                  TABLE 5                                                          ______________________________________                                                              MS                                                                             (m/z)                                                     ______________________________________                                         2-(N-cyclohexyl-N-methylamino)-5-((2,6-                                                               378                                                     dichlorophenyl)carbonylamino)pyridine                                          2-(N-cyclohexyl-N-methylamino)-5-((2-                                                                 344                                                     chlorophenyl)carbonylamino)pyridine                                            2-(N-cyclohexyl-N-methylamino)-5-((2-                                                                 323                                                     methylphenyl)carbonylamino)pyridine                                            2-(N-cyclohexyl-N-methylamino)-5-((2,6-                                                               337                                                     dimethylphenyl)carbonylamino)pyridine                                          2-(2,4-dimethylphenyl)-5-((2,6-                                                                       359                                                     dimethylphenyl)carbonylamino)pyridine                                          2-(2,4-dimethylphenyl)-5-((2-                                                                         345                                                     methylphenyl)carbonylamino)pyridine                                            2-(2,4-dimethylphenyl)-5-((2-                                                                         366                                                     chlorophenyl)carbonylamino)pyridine                                            2-(2,4-dimethylphenyl)-5-((2-                                                                         349                                                     fluorophenyl)carbonylamino)pyridine                                            2-(2,4-dimethylphenyl)-5-((2,6-                                                                       400                                                     dichlorophenyl)carbonylamino)pyridine                                          ______________________________________                                    

EXAMPLE 14 ##STR17## Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine

2-(4-Chloro-2-methyl-phenoxy)-5-aminopyridine (2.15 g, 9.16 mmol) was combined with powdered sodium hydroxide (1.46 g, 36.6 mmol), potassium carbonate (1.27 g, 9.16 mmol), tetrabutyl ammonium bromide (60 mg, 0.18 mmol) and toluene (10 mL) was stirred for 1 hour at 35° C. A solution of dimethyl sulfate (0.91 mL, 9.6 mmol) dissolved in toluene (5 mL) was added slowly. The mixture was heated at 35° C. for 20 hours. After cooling, the solids were removed by filtration and the solvent was concentrated in vacuo. The desired material was purified by chromatography on SiO₂ using 30% ethyl acetate/hexanes as eluent. MS (m/z): 248/250 (M+H)⁺ ; C₁₃ H₁₃ N₂ OCl requires 249.

EXAMPLE 15 ##STR18## Preparation of 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine (32 mg, 0.13 mmol) dissolved in methylene chloride (0.25 mL) was treated with triethylamine (0.026 mL, 0.18 mmol) followed by a solution of 2,6-dichlorobenzoyl chloride (31 mg, 0.15 mmol) dissolved in methylene chloride (0.15 mL). The reaction mixture was shaken at 22° C. for 18 hours followed by quenching with saturated aqueous NH₄ Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na₂ SO₄ then concentrated in vacuo. The crude product was purified by chromatography on SiO₂ using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 422/424 (M+H)⁺ ; C₂₀ H₁₅ N₂ O₂ Cl₃ requires 422.

EXAMPLE 16 ##STR19## Preparation of 2-Chloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-Chloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared from 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine and 2-chlorobenzoyl chloride in the same manner as 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared.

EXAMPLE 17 ##STR20## Preparation of 2-Methyl-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-Methyl-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared from 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine and 2-methylbenzoyl chloride in the same manner as 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared.

EXAMPLE 18 ##STR21## General procedure for the synthesis of 2-substituted-5-acylamino-pyridines

A solution of the 2-substituted-5-aminopyridine (10 mmol), triethylamine (20 mmol) and an acid chloride (20 mmol) in ethanol free chloroform (250 mL) was shaken for 16 hours. The mixture was then diluted with saturated aqueous sodium hydrogencarbonate (50 mL) and dichloromethane (500 mL), and shaken for 30 min. The mixture was then filtered through anhydrous magnesium sulfate, washing with dichloromethane (250 mL). Concentration of the filtrate under reduced pressure afforded the desired 2-substituted-5-acylamino-pyridines.

The compounds listed in Table 6 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride according to the general procedure above.

                  TABLE 6                                                          ______________________________________                                                                        MS                                              R.sup.1 X     R.sup.3          (m/z)                                           ______________________________________                                         4-chloro-2-   4-biphenyl       415                                             methylphenoxy                                                                  4-chloro-2-   3,4-dimethoxyphenyl                                                                             319                                             methylphenoxy                                                                  4-chloro-2-   2-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-2-   2,4-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-2-   4-cyanophenyl    364                                             methylphenoxy                                                                  4-chloro-2-   3-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-2-   3-cyanophenyl    364                                             methylphenoxy                                                                  4-chloro-2-   2-naphthyl       389                                             methylphenoxy                                                                  4-chloro-2-   2-methoxyphenyl  369                                             methylphenoxy                                                                  4-chloro-2-   3,4,5-trimethylphenyl                                                                           429                                             methylphenoxy                                                                  4-chloro-2-   4-nitrophenyl    384                                             methylphenoxy                                                                  4-chloro-2-   3,4-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-2-   5-nitrofuran-2-yl                                                                               374                                             methylphenoxy                                                                  4-chloro-2-   3-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-2-   3-pyridyl        340                                             methylphenoxy                                                                  4-chloro-2-   2-ethoxynaphth-1-yl                                                                             433                                             methylphenoxy                                                                  4-chloro-2-   2,3-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-2-   3-nitrophenyl    384                                             methylphenoxy                                                                  4-chloro-2-   6-chloropyrid-3-yl                                                                              374                                             methylphenoxy                                                                  4-chloro-2-   4-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-2-   2-fluoro-4-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-2-   2-acetoxyphenyl  397                                             methylphenoxy                                                                  4-chloro-2-   5-methylisoxazol-3-yl                                                                           344                                             methylphenoxy                                                                  4-chloro-2-   2-(phenylthio)pyrid-3-yl                                                                        448                                             methylphenoxy                                                                  4-chloro-2-   2-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-2-   1-phenyl-5-propyl-pyrazin-                                                                      447                                             methylphenoxy 4-yl                                                             4-chloro-2-   2-ethoxyphenyl   383                                             methylphenoxy                                                                  4-chloro-2-   3-chlorothien-2-yl                                                                              379                                             methylphenoxy                                                                  4-chloro-2-   3-bromothien-2-yl                                                                               424                                             methylphenoxy                                                                  4-chloro-2-   1-(2-(2-methyl)propyl)-3-                                                                       399                                             methylphenoxy methylpyrazol-5-yl                                               4-chloro-2-   3,5-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-2-   2-(propylthio)pyridin-3-yl                                                                      414                                             methylphenoxy                                                                  4-chloro-2-   2-(ethylthio)pyridin-3-yl                                                                       400                                             methylphenoxy                                                                  4-chloro-2-   3-bromopyridin-5-yl                                                                             419                                             methylphenoxy                                                                  4-chloro-2-   4-methyl-1,2,3-thiadiazol-                                                                      361                                             methylphenoxy 5-yl                                                             4-chloro-2-   1-methyl-3-(2-(2-                                                                               399                                             methylphenoxy methyl)propyl)pyrazol-5-yl                                       4-chloro-2-   3-chlorobenzo[b]thiophen-                                                                       429                                             methylphenoxy 2-yl                                                             4-chloro-2-   4-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-2-   4-methyl-2-phenyl-1,2,3-                                                                        420                                             methylphenoxy triazol-5-yl                                                     4-chloro-2-   benzo[b]thiophen-2-yl                                                                           395                                             methylphenoxy                                                                  4-chloro-2-   3,4-dimethylphenyl                                                                              367                                             methylphenoxy                                                                  4-chloro-2-   2-(phenoxy)pyridin-3-yl                                                                         432                                             methylphenoxy                                                                  4-chloro-2-   2-(methylthio)pyridin-3-yl                                                                      386                                             methylphenoxy                                                                  4-chloro-2-   5-methyl-3-phenylisoxazol-                                                                      420                                             methylphenoxy 4-yl                                                             4-chloro-2-   4-chloro-1,3-dimethyl                                                                           442                                             methylphenoxy pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-2-   2-chloro-6-methylpyridin-                                                                       388                                             methylphenoxy 4-yl                                                             4-chloro-2-   3,5-dimethylisoxazol-4-yl                                                                       358                                             methylphenoxy                                                                  4-chloro-2-   1-naphthyl       389                                             methylphenoxy                                                                  4-chloro-2-   2-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-2-   4-propylphenyl   381                                             methylphenoxy                                                                  4-chloro-2-   4-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-2-   3-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-2-   2,6-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-2-   2-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-2-   3-(chloromethyl)phenyl                                                                          387                                             methylphenoxy                                                                  4-chloro-2-   4-(2-(2-methyl)  395                                             methylphenoxy propyl)phenyl                                                    4-chloro-2-   3-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-2-   2-nitrophenyl    384                                             methylphenoxy                                                                  4-chloro-2-   3,5-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-2-   2,6-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-2-   2,4-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-2-   4-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-2-   4-butylphenyl    395                                             methylphenoxy                                                                  4-chloro-2-   2-methylphenyl   353                                             methylphenoxy                                                                  4-chloro-2-   phenyl           339                                             methylphenoxy                                                                  4-chloro-2-   4-ethylphenyl    367                                             methylphenoxy                                                                  4-chloro-2-   2,3-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-2-   2,6-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-2-   2,5-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-2-   4-ethoxyphenyl   383                                             methylphenoxy                                                                  4-chloro-2-   2,4,6-trichlorophenyl                                                                           442                                             methylphenoxy                                                                  4-chloro-2-   3-methylphenyl   353                                             methylphenoxy                                                                  4-chloro-2-   2-fluoro-5-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-2-   3-methoxyphenyl  369                                             methylphenoxy                                                                  4-chloro-2-   thien-2-yl       345                                             methylphenoxy                                                                  4-chloro-2-   2-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-2-   4-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-2-   4-fluoro-3-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-2-   3-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-2-   9-fluorenon-4-yl 441                                             methylphenoxy                                                                  4-chloro-2-   isoxazol-5-yl    330                                             methylphenoxy                                                                  4-chloro-2-   benzofuroxan-5-yl                                                                               397                                             methylphenoxy                                                                  4-chloro-2-   2-chloropyrid-3-yl                                                                              374                                             methylphenoxy                                                                  4-chloro-2-   3,5-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-2-   2-(4-            446                                             methylphenoxy methylphenoxy)pyridin-3-yl                                       4-chloro-2-   pyridin-4-yl     340                                             methylphenoxy                                                                  4-chloro-2-   anthraquinon-2-yl                                                                               469                                             methylphenoxy                                                                  4-chloro-2-   2-iodophenyl     465                                             methylphenoxy                                                                  1-naphthoxy   4-biphenyl       416                                             1-naphthoxy   3,4-dimethoxyphenyl                                                                             400                                             1-naphthoxy   2-(trifluoromethyl)phenyl                                                                       408                                             1-naphthoxy   2,4-difluorophenyl                                                                              376                                             1-naphthoxy   4-cyanophenyl    365                                             1-naphthoxy   3-(trifluoromethyl)phenyl                                                                       408                                             1-naphthoxy   3-cyanophenyl    365                                             1-naphthoxy   2-naphthyl       390                                             1-naphthoxy   2-methoxyphenyl  370                                             1-naphthoxy   3,4,5-trimethylphenyl                                                                           430                                             1-naphthoxy   4-nitrophenyl    385                                             1-naphthoxy   3,4-dichlorophenyl                                                                              409                                             1-naphthoxy   5-nitrofuran-2-yl                                                                               375                                             1-naphthoxy   3-bromophenyl    419                                             1-naphthoxy   3-pyridyl        341                                             1-naphthoxy   2-ethoxynaphth-1-yl                                                                             334                                             1-naphthoxy   2,3-dichlorophenyl                                                                              409                                             1-naphthoxy   3-nitrophenyl    385                                             1-naphthoxy   6-chloropyrid-3-yl                                                                              376                                             1-naphthoxy   4-(trifluoromethoxy)phenyl                                                                      424                                             1-naphthoxy   2-fluoro-4-      426                                                           (trifluoromethyl)phenyl                                          1-naphthoxy   3-bromothiophenyl                                                                               425                                             1-naphthoxy   2-acetoxyphenyl  398                                             1-naphthoxy   5-methylisoxazol-3-yl                                                                           345                                             1-naphthoxy   2-(phenylthio)pyrid-3-yl                                                                        449                                             1-naphthoxy   2-(trifluoromethoxy)phenyl                                                                      424                                             1-naphthoxy   1-phenyl-5-propylpyrazin-                                                                       448                                                           4-yl                                                             1-naphthoxy   2-ethoxyphenyl   384                                             1-naphthoxy   3-chlorothien-2-yl                                                                              381                                             1-naphthoxy   1-(2-(2-methyl)propyl)-3-                                                                       400                                                           methylpyrazol-5-yl                                               1-naphthoxy   3,5-dichlorophenyl                                                                              409                                             1-naphthoxy   2-(propylthio)pyridin-3-yl                                                                      415                                             1-naphthoxy   2-(ethylthio)pyridin-3-yl                                                                       401                                             1-naphthoxy   3-bromopyridin-5-yl                                                                             420                                             1-naphthoxy   4-methyl-1,2,3-thiadiazol-                                                                      362                                                           5-yl                                                             1-naphthoxy   1-methyl-3-(2-(2-                                                                               400                                                           methyl)propyl)pyrazol-5-yl                                       1-naphthoxy   3-chlorobenzo[b]thiophen-                                                                       431                                                           2-yl                                                             1-naphthoxy   4-chlorophenyl   375                                             1-naphthoxy   4-methyl-2-phenyl-1,2,3-                                                                        421                                                           triazol-5-yl                                                     1-naphthoxy   benzo[b]thiophen-2-yl                                                                           396                                             1-naphthoxy   3,4-dimethylphenyl                                                                              368                                             1-naphthoxy   2-(phenoxy)pyridin-3-yl                                                                         433                                             1-naphthoxy   2-(methylthio)pyridin-3-yl                                                                      387                                             1-naphthoxy   5-methyl-3-phenylisoxazol-                                                                      421                                                           4-yl                                                             1-naphthoxy   4-chloro-1,3-dimethyl                                                                           444                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               1-naphthoxy   2-chloro-6-methylpyridin-                                                                       390                                                           4-yl                                                             1-naphthoxy   3,5-dimethylisoxazol-4-yl                                                                       359                                             1-naphthoxy   1-naphthyl       390                                             1-naphthoxy   2-fluorophenyl   358                                             1-naphthoxy   4-propylphenyl   382                                             1-naphthoxy   4-(trifluoromethyl)phenyl                                                                       408                                             1-naphthoxy   3-fluorophenyl   358                                             1-naphthoxy   2,6-difluorophenyl                                                                              376                                             1-naphthoxy   2-chlorophenyl   375                                             1-naphthoxy   3-(chloromethyl)phenyl                                                                          389                                             1-naphthoxy   4-(2-(2-         396                                                           methyl)propyl)phenyl                                             1-naphthoxy   3-chlorophenyl   375                                             1-naphthoxy   2-nitrophenyl    385                                             1-naphthoxy   3,5-dimethoxyphenyl                                                                             400                                             1-naphthoxy   2,6-dichlorophenyl                                                                              409                                             1-naphthoxy   2,4-dichlorophenyl                                                                              409                                             1-naphthoxy   4-fluorophenyl   358                                             1-naphthoxy   4-butylphenyl    396                                             1-naphthoxy   2-methylphenyl   354                                             1-naphthoxy   phenyl           340                                             1-naphthoxy   4-ethylphenyl    368                                             1-naphthoxy   2,3-difluorophenyl                                                                              376                                             1-naphthoxy   2,6-dimethoxyphenyl                                                                             400                                             1-naphthoxy   3,4-difluorophenyl                                                                              376                                             1-naphthoxy   2,5-difluorophenyl                                                                              376                                             1-naphthoxy   4-ethoxyphenyl   384                                             1-naphthoxy   2,4,6-trichlorophenyl                                                                           444                                             1-naphthoxy   3-methylphenyl   354                                             1-naphthoxy   2-fluoro-5-      426                                                           (trifluoromethyl)phenyl                                          1-naphthoxy   3-methoxyphenyl  370                                             1-naphthoxy   thien-2-yl       346                                             1-naphthoxy   2-bromophenyl    419                                             1-naphthoxy   4-bromophenyl    419                                             1-naphthoxy   4-fluoro-3-      426                                                           (trifluoromethyl)phenyl                                          1-naphthoxy   3-(trifluoromethoxy)phenyl                                                                      424                                             1-naphthoxy   9-fluorenon-4-yl 442                                             1-naphthoxy   isoxazol-5-yl    331                                             1-naphthoxy   benzofuroxan-5-yl                                                                               398                                             1-naphthoxy   2-chloropyrid-3-yl                                                                              376                                             1-naphthoxy   3,5-difluorophenyl                                                                              376                                             1-naphthoxy   2-(4-            447                                                           methylphenoxy)pyridin-3-yl                                       1-naphthoxy   pyridin-4-yl     341                                             1-naphthoxy   anthraquinon-2-yl                                                                               470                                             1-naphthoxy   2-iodophenyl     466                                             2-(2-propyl)phenoxy                                                                          4-biphenyl       408                                             2-(2-propyl)phenoxy                                                                          3,4-dimethoxyphenyl                                                                             392                                             2-(2-propyl)phenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       400                                             2-(2-propyl)phenoxy                                                                          2,4-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          4-cyanophenyl    357                                             2-(2-propyl)phenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       400                                             2-(2-propyl)phenoxy                                                                          3-cyanophenyl    357                                             2-(2-propyl)phenoxy                                                                          2-naphthyl       382                                             2-(2-propyl)phenoxy                                                                          2-methoxyphenyl  362                                             2-(2-propyl)phenoxy                                                                          3,4,5,-trimethylphenyl                                                                          422                                             2-(2-propyl)phenoxy                                                                          4-nitrophenyl    377                                             2-(2-propyl)phenoxy                                                                          3,4-dichlorophenyl                                                                              401                                             2-(2-propyl)phenoxy                                                                          5-nitrofuran-2-yl                                                                               367                                             2-(2-propyl)phenoxy                                                                          3-bromophenyl    411                                             2-(2-propyl)phenoxy                                                                          3-pyridyl        333                                             2-(2-propyl)phenoxy                                                                          2-ethoxynaphth-1-yl                                                                             426                                             2-(2-propyl)phenoxy                                                                          2,3-dichlorophenyl                                                                              401                                             2-(2-propyl)phenoxy                                                                          3-nitrophenyl    377                                             2-(2-propyl)phenoxy                                                                          6-chloropyrid-3-yl                                                                              368                                             2-(2-propyl)phenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      416                                             2-(2-propyl)phenoxy                                                                          2-fluoro-4-      418                                                           (trifluoromethyl)phenyl                                          2-(2-propyl)phenoxy                                                                          3-bromothiophenyl                                                                               417                                             2-(2-propyl)phenoxy                                                                          2-acetoxyphenyl  390                                             2-(2-propyl)phenoxy                                                                          5-methylisoxazol-3-yl                                                                           337                                             2-(2-propyl)phenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        442                                             2-(2-propyl)phenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      416                                             2-(2-propyl)phenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       441                                                           4-yl                                                             2-(2-propyl)phenoxy                                                                          2-ethoxyphenyl   376                                             2-(2-propyl)phenoxy                                                                          3-chlorothien-2-yl                                                                              373                                             2-(2-propyl)phenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       392                                                           methylpyrazol-5-yl                                               2-(2-propyl)phenoxy                                                                          3,5-dichlorophenyl                                                                              401                                             2-(2-propyl)phenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      407                                             2-(2-propyl)phenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       393                                             2-(2-propyl)phenoxy                                                                          3-bromopyridin-5-yl                                                                             412                                             2-(2-propyl)phenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      354                                                           5-yl                                                             2-(2-propyl)phenoxy                                                                          1-methyl-3-(2-(2-                                                                               392                                                           methyl)propyl)pyrazol-5-yl                                       2-(2-propyl)phenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       423                                                           2-yl                                                             2-(2-propyl)phenoxy                                                                          4-chlorophenyl   367                                             2-(2-propyl)phenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        413                                                           triazol-5-yl                                                     2-(2-propyl)phenoxy                                                                          benzo[b]thiophen-2-yl                                                                           388                                             2-(2-propyl)phenoxy                                                                          3,4-dimethylphenyl                                                                              360                                             2-(2-propyl)phenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         425                                             2-(2-propyl)phenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      379                                             2-(2-propyl)phenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      413                                                           4-yl                                                             2-(2-propyl)phenoxy                                                                          4-chloro-1,3-    436                                                           dimethylpyrazolo[3,4-                                                          b]pyridin-3-yl                                                   2-(2-propyl)phenoxy                                                                          2-chloro-6-methylpyridin-                                                                       382                                                           4-yl                                                             2-(2-propyl)phenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       351                                             2-(2-propyl)phenoxy                                                                          1-naphthyl       382                                             2-(2-propyl)phenoxy                                                                          2-fluorophenyl   350                                             2-(2-propyl)phenoxy                                                                          4-propylphenyl   374                                             2-(2-propyl)phenoxy                                                                          4-(trifluoromethyl)phenyl                                                                       400                                             2-(2-propyl)phenoxy                                                                          3-fluorophenyl   350                                             2-(2-propyl)phenoxy                                                                          2,6-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          2-chlorophenyl   367                                             2-(2-propyl)phenoxy                                                                          3-(chloromethyl)phenyl                                                                          381                                             2-(2-propyl)phenoxy                                                                          4-(2-(2-         388                                                           methyl)propyl)phenyl                                             2-(2-propyl)phenoxy                                                                          3-chlorophenyl   367                                             2-(2-propyl)phenoxy                                                                          2-nitrophenyl    377                                             2-(2-propyl)phenoxy                                                                          3,5-dimethoxyphenyl                                                                             392                                             2-(2-propyl)phenoxy                                                                          2,6-dichlorophenyl                                                                              401                                             2-(2-propyl)phenoxy                                                                          2,4-dichlorophenyl                                                                              401                                             2-(2-propyl)phenoxy                                                                          4-fluorophenyl   350                                             2-(2-propyl)phenoxy                                                                          4-butylphenyl    388                                             2-(2-propyl)phenoxy                                                                          2-methylphenyl   346                                             2-(2-propyl)phenoxy                                                                          phenyl           332                                             2-(2-propyl)phenoxy                                                                          4-ethylphenyl    360                                             2-(2-propyl)phenoxy                                                                          2,3-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          2,6-dimethoxyphenyl                                                                             392                                             2-(2-propyl)phenoxy                                                                          3,4-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          2,5-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          4-ethoxyphenyl   376                                             2-(2-propyl)phenoxy                                                                          2,4,6-trichlorophenyl                                                                           436                                             2-(2-propyl)phenoxy                                                                          3-methylphenyl   346                                             2-(2-propyl)phenoxy                                                                          2-fluoro-5-      418                                                           (trifluoromethyl)phenyl                                          2-(2-propyl)phenoxy                                                                          3-methoxyphenyl  362                                             2-(2-propyl)phenoxy                                                                          thien-2-yl       338                                             2-(2-propyl)phenoxy                                                                          2-bromophenyl    411                                             2-(2-propyl)phenoxy                                                                          4-bromophenyl    411                                             2-(2-propyl)phenoxy                                                                          4-fluoro-3-      418                                                           (trifluoromethyl)phenyl                                          2-(2-propyl)phenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      416                                             2-(2-propyl)phenoxy                                                                          9-fluorenon-4-yl 434                                             2-(2-propyl)phenoxy                                                                          isoxazol-5-yl    323                                             2-(2-propyl)phenoxy                                                                          benzofuroxan-5-yl                                                                               390                                             2-(2-propyl)phenoxy                                                                          2-chloropyrid-3-yl                                                                              368                                             2-(2-propyl)phenoxy                                                                          3,5-difluorophenyl                                                                              368                                             2-(2-propyl)phenoxy                                                                          2-(4-            439                                                           methylphenoxy)pyridin-3-yl                                       2-(2-propyl)phenoxy                                                                          pyridin-4-yl     333                                             2-(2-propyl)phenoxy                                                                          anthraquinon-2-yl                                                                               462                                             2-(2-propyl)phenoxy                                                                          2-iodophenyl     458                                             3-fluoro-5-   4-biphenyl       398                                             methylphenoxy                                                                  3-fluoro-5-   3,4-dimethoxyphenyl                                                                             382                                             methylphenoxy                                                                  3-fluoro-5-   2-(trifluoromethyl)phenyl                                                                       390                                             methylphenoxy                                                                  3-fluoro-5-   2,4-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   4-cyanophenyl    347                                             methylphenoxy                                                                  3-fluoro-5-   3-(trifluoromethyl)phenyl                                                                       390                                             methylphenoxy                                                                  3-fluoro-5-   3-cyanophenyl    347                                             methylphenoxy                                                                  3-fluoro-5-   2-naphthyl       372                                             methylphenoxy                                                                  3-fluoro-5-   2-methoxyphenyl  352                                             methylphenoxy                                                                  3-fluoro-5-   3,4,5,-trimethylphenyl                                                                          412                                             methylphenoxy                                                                  3-fluoro-5-   4-nitrophenyl    367                                             methylphenoxy                                                                  3-fluoro-5-   3,4-dichlorophenyl                                                                              391                                             methylphenoxy                                                                  3-fluoro-5-   5-nitrofuran-2-yl                                                                               357                                             methylphenoxy                                                                  3-fluoro-5-   3-bromophenyl    401                                             methylphenoxy                                                                  3-fluoro-5-   3-pyridyl        323                                             methylphenoxy                                                                  3-fluoro-5-   2-ethoxynaphth-1-yl                                                                             416                                             methylphenoxy                                                                  3-fluoro-5-   2,3-dichlorophenyl                                                                              391                                             methylphenoxy                                                                  3-fluoro-5-   3-nitrophenyl    367                                             methylphenoxy                                                                  3-fluoro-5-   6-chloropyrid-3-yl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   4-(trifluoromethoxy)phenyl                                                                      406                                             methylphenoxy                                                                  3-fluoro-5-   2-fluoro-4-      408                                             methylphenoxy (trifluoromethyl)phenyl                                          3-fluoro-5-   3-bromothienyl   407                                             methylphenoxy                                                                  3-fluoro-5-   2-acetoxyphenyl  380                                             methylphenoxy                                                                  3-fluoro-5-   5-methylisoxazol-3-yl                                                                           327                                             methylphenoxy                                                                  3-fluoro-5-   2-(phenylthio)pyrid-3-yl                                                                        431                                             methylphenoxy                                                                  3-fluoro-5-   2-(trifluoromethoxy)phenyl                                                                      406                                             methylphenoxy                                                                  3-fluoro-5-   1-phenyl-5-propylpyrazin-                                                                       430                                             methylphenoxy 4-yl                                                             3-fluoro-5-   2-ethoxyphenyl   366                                             methylphenoxy                                                                  3-fluoro-5-   3-chlorothien-2-yl                                                                              363                                             methylphenoxy                                                                  3-fluoro-5-   1-(2-(2-methyl)propyl)-3-                                                                       382                                             methylphenoxy methylpyrazol-5-yl                                               3-fluoro-5-   3,5-dichlorophenyl                                                                              391                                             methylphenoxy                                                                  3-fluoro-5-   2-(propylthio)pyridin-3-yl                                                                      397                                             methylphenoxy                                                                  3-fluoro-5-   2-(ethylthio)pyridin-3-yl                                                                       383                                             methylphenoxy                                                                  3-fluoro-5-   3-bromopyridin-5-yl                                                                             402                                             methylphenoxy                                                                  3-fluoro-5-   4-methyl-1,2,3-thiadiazol-                                                                      344                                             methylphenoxy 5-yl                                                             3-fluoro-5-   1-methyl-3-(2-(2-                                                                               382                                             methylphenoxy methyl)propyl)pyrazol-5-yl                                       3-fluoro-5-   3-chlorobenzo[b]thiophen-                                                                       413                                             methylphenoxy 2-yl                                                             3-fluoro-5-   4-chlorophenyl   357                                             methylphenoxy                                                                  3-fluoro-5-   4-methyl-2-phenyl-1,2,3-                                                                        403                                             methylphenoxy triazol-5-yl                                                     3-fluoro-5-   benzo[b]thiophen-2-yl                                                                           378                                             methylphenoxy                                                                  3-fluoro-5-   3,4-dimethylphenyl                                                                              350                                             methylphenoxy                                                                  3-fluoro-5-   2-(phenoxy)pyridin-3-yl                                                                         415                                             methylphenoxy                                                                  3-fluoro-5-   2-(methylthio)pyridin-3-yl                                                                      369                                             methylphenoxy                                                                  3-fluoro-5-   5-methyl-3-phenylisoxazol-                                                                      403                                             methylphenoxy 4-yl                                                             3-fluoro-5-   4-chloro-1,3-dimethyl                                                                           426                                             methylphenoxy pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               3-fluoro-5-   2-chloro-6-methylpyridin-                                                                       372                                             methylphenoxy 4-yl                                                             3-fluoro-5-   3,5-dimethylisoxazol-4-yl                                                                       341                                             methylphenoxy                                                                  3-fluoro-5-   1-naphthyl       372                                             methylphenoxy                                                                  3-fluoro-5-   2-fluorophenyl   340                                             methylphenoxy                                                                  3-fluoro-5-   4-propylphenyl   364                                             methylphenoxy                                                                  3-fluoro-5-   4-(trifluoromethyl)phenyl                                                                       390                                             methylphenoxy                                                                  3-fluoro-5-   3-fluorophenyl   340                                             methylphenoxy                                                                  3-fluoro-5-   2,6-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   2-chlorophenyl   357                                             methylphenoxy                                                                  3-fluoro-5-   3-(chloromethyl)phenyl                                                                          371                                             methylphenoxy                                                                  3-fluoro-5-   4-(2-(2-         378                                             methylphenoxy methyl)propyl)phenyl                                             3-fluoro-5-   3-chlorophenyl   357                                             methylphenoxy                                                                  3-fluoro-5-   2-nitrophenyl    367                                             methylphenoxy                                                                  3-fluoro-5-   3,5-dimethoxyphenyl                                                                             382                                             methylphenoxy                                                                  3-fluoro-5-   2,6-dichlorophenyl                                                                              391                                             methylphenoxy                                                                  3-fluoro-5-   2,4-dichlorophenyl                                                                              391                                             methylphenoxy                                                                  3-fluoro-5-   4-fluorophenyl   340                                             methylphenoxy                                                                  3-fluoro-5-   4-butylphenyl    378                                             methylphenoxy                                                                  3-fluoro-5-   2-methylphenyl   336                                             methylphenoxy                                                                  3-fluoro-5-   phenyl           322                                             methylphenoxy                                                                  3-fluoro-5-   4-ethylphenyl    350                                             methylphenoxy                                                                  3-fluoro-5-   2,3-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   2,6-dimethoxyphenyl                                                                             382                                             methylphenoxy                                                                  3-fluoro-5-   3,4-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   2,5-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   4-ethoxyphenyl   366                                             methylphenoxy                                                                  3-fluoro-5-   2,4,6-trichlorophenyl                                                                           426                                             methylphenoxy                                                                  3-fluoro-5-   3-methylphenyl   336                                             methylphenoxy                                                                  3-fluoro-5-   2-fluoro-5-      408                                             methylphenoxy (trifluoromethyl)phenyl                                          3-fluoro-5-   3-methoxyphenyl  352                                             methylphenoxy                                                                  3-fluoro-5-   thien-2-yl       328                                             methylphenoxy                                                                  3-fluoro-5-   2-bromophenyl    401                                             methylphenoxy                                                                  3-fluoro-5-   4-bromophenyl    401                                             methylphenoxy                                                                  3-fluoro-5-   4-fluoro-3-      408                                             methylphenoxy (trifluoromethyl)phenyl                                          3-fluoro-5-   3-(trifluoromethoxy)phenyl                                                                      406                                             methylphenoxy                                                                  3-fluoro-5-   9-fluorenon-4-yl 424                                             methylphenoxy                                                                  3-fluoro-5-   isoxazol-5-yl    313                                             methylphenoxy                                                                  3-fluoro-5-   benzofuroxan-5-yl                                                                               380                                             methylphenoxy                                                                  3-fluoro-5-   2-chloropyrid-3-yl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   3,5-difluorophenyl                                                                              358                                             methylphenoxy                                                                  3-fluoro-5-   2-(4-            429                                             methylphenoxy methylphenoxy)pyridin-3-yl                                       3-fluoro-5-   pyridin-4-yl     323                                             methylphenoxy                                                                  3-fluoro-5-   anthraquinon-2-yl                                                                               452                                             methylphenoxy                                                                  3-fluoro-5-   2-iodophenyl     448                                             methylphenoxy                                                                  2-methylpyrid-3-yloxy                                                                        4-biphenyl       381                                             2-methylpyrid-3-yloxy                                                                        3,4-dimethoxyphenyl                                                                             365                                             2-methylpyrid-3-yloxy                                                                        2-(trifluoromethyl)phenyl                                                                       373                                             2-methylpyrid-3-yloxy                                                                        2,4-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        4-cyanophenyl    330                                             2-methylpyrid-3-yloxy                                                                        3-(trifluoromethyl)phenyl                                                                       373                                             2-methylpyrid-3-yloxy                                                                        3-cyanophenyl    330                                             2-methylpyrid-3-yloxy                                                                        2-naphthyl       3 55                                            2-methylpyrid-3-yloxy                                                                        2-methoxyphenyl  335                                             2-methylpyrid-3-yloxy                                                                        3,4,5-trimethylphenyl                                                                           395                                             2-methylpyrid-3-yloxy                                                                        4-nitrophenyl    350                                             2-methylpyrid-3-yloxy                                                                        3,4-dichlorophenyl                                                                              374                                             2-methylpyrid-3-yloxy                                                                        5-nitrofuran-2-yl                                                                               340                                             2-methylpyrid-3-yloxy                                                                        3-bromophenyl    384                                             2-methylpyrid-3-yloxy                                                                        3-pyridyl        306                                             2-methylpyrid-3-yloxy                                                                        2-ethoxynaphth-1-yl                                                                             399                                             2-methylpyrid-3-yloxy                                                                        2,3-dichlorophenyl                                                                              374                                             2-methylpyrid-3-yloxy                                                                        3-nitrophenyl    350                                             2-methylpyrid-3-yloxy                                                                        6-chloropyrid-3-yl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        4-(trifluoromethoxy)phenyl                                                                      389                                             2-methylpyrid-3-yloxy                                                                        2-fluoro-4-      391                                                           (trifluoromethyl)phenyl                                          2-methylpyrid-3-yloxy                                                                        3-bromothienyl   390                                             2-methylpyrid-3-yloxy                                                                        2-acetoxyphenyl  363                                             2-methylpyrid-3-yloxy                                                                        5-methylisoxazol-3-yl                                                                           310                                             2-methylpyrid-3-yloxy                                                                        2-(phenylthio)pyrid-3-yl                                                                        414                                             2-methylpyrid-3-yloxy                                                                        2-(trifluoromethoxy)phenyl                                                                      389                                             2-methylpyrid-3-yloxy                                                                        1-phenyl-5-propylpyrazin-                                                                       413                                                           4-yl                                                             2-methylpyrid-3-yloxy                                                                        2-ethoxyphenyl   349                                             2-methylpyrid-3-yloxy                                                                        3-chlorothien-2-yl                                                                              346                                             2-methylpyrid-3-yloxy                                                                        1-(2-(2-methyl)propyl)-3-                                                                       365                                                           methylpyrazol-5-yl                                               2-methylpyrid-3-yloxy                                                                        3,5-dichlorophenyl                                                                              374                                             2-methylpyrid-3-yloxy                                                                        2-(propylthio)pyridin-3-yl                                                                      380                                             2-methylpyrid-3-yloxy                                                                        2-(ethylthio)pyridin-3-yl                                                                       366                                             2-methylpyrid-3-yloxy                                                                        3-bromopyridin-5-yl                                                                             385                                             2-methylpyrid-3-yloxy                                                                        4-methyl-1,2,3-thiadiazol-                                                                      327                                                           5-yl                                                             2-methylpyrid-3-yloxy                                                                        1-methyl-3-(2-(2-                                                                               365                                                           methyl)propyl)pyrazol-5-yl                                       2-methylpyrid-3-yloxy                                                                        3-chlorobenzo[b]thiophen-                                                                       396                                                           2-yl                                                             2-methylpyrid-3-yloxy                                                                        4-chlorophenyl   340                                             2-methylpyrid-3-yloxy                                                                        4-methyl-2-phenyl-1,2,3-                                                                        386                                                           triazol-5-yl                                                     2-methylpyrid-3-yloxy                                                                        benzo[b]thiophen-2-yl                                                                           361                                             2-methylpyrid-3-yloxy                                                                        3,4-dimethylphenyl                                                                              333                                             2-methylpyrid-3-yloxy                                                                        2-(phenoxy)pyridin-3-yl                                                                         398                                             2-methylpyrid-3-yloxy                                                                        2-(methylthio)pyridin-3-yl                                                                      352                                             2-methylpyrid-3-yloxy                                                                        5-methyl-3-phenylisoxazol-                                                                      386                                                           4-yl                                                             2-methylpyrid-3-yloxy                                                                        4-chloro-1,3-dimethyl                                                                           409                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2-methylpyrid-3-yloxy                                                                        2-chloro-6-methylpyridin-                                                                       355                                                           4-yl                                                             2-methylpyrid-3-yloxy                                                                        3,5-dimethylisoxazol-4-yl                                                                       324                                             2-methylpyrid-3-yloxy                                                                        1-naphthyl       355                                             2-methylpyrid-3-yloxy                                                                        2-fluorophenyl   323                                             2-methylpyrid-3-yloxy                                                                        4-propylphenyl   347                                             2-methylpyrid-3-yloxy                                                                        4-(trifluoromethyl)phenyl                                                                       373                                             2-methylpyrid-3-yloxy                                                                        3-fluorophenyl   323                                             2-methylpyrid-3-yloxy                                                                        2,6-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        2-chlorophenyl   340                                             2-methylpyrid-3-yloxy                                                                        3-(chloromethyl)phenyl                                                                          354                                             2-methylpyrid-3-yloxy                                                                        4-(2-(2-         361                                                           methyl)propyl)phenyl                                             2-methylpyrid-3-yloxy                                                                        3-chlorophenyl   340                                             2-methylpyrid-3-yloxy                                                                        2-nitrophenyl    350                                             2-methylpyrid-3-yloxy                                                                        3,5-dimethoxyphenyl                                                                             365                                             2-methylpyrid-3-yloxy                                                                        2,6-dichlorophenyl                                                                              374                                             2-methylpyrid-3-yloxy                                                                        2,4-dichlorophenyl                                                                              374                                             2-methylpyrid-3-yloxy                                                                        4-fluorophenyl   323                                             2-methylpyrid-3-yloxy                                                                        4-butylphenyl    361                                             2-methylpyrid-3-yloxy                                                                        2-methylphenyl   319                                             2-methylpyrid-3-yloxy                                                                        phenyl           305                                             2-methylpyrid-3-yloxy                                                                        4-ethylphenyl    333                                             2-methylpyrid-3-yloxy                                                                        2,3-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        2,6-dimethoxyphenyl                                                                             365                                             2-methylpyrid-3-yloxy                                                                        3,4-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        2,5-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        4-ethoxyphenyl   349                                             2-methylpyrid-3-yloxy                                                                        2,4,6-trichlorophenyl                                                                           409                                             2-methylpyrid-3-yloxy                                                                        3-methylphenyl   319                                             2-methylpyrid-3-yloxy                                                                        2-fluoro-5-      391                                                           (trifluoromethyl)phenyl                                          2-methylpyrid-3-yloxy                                                                        3-methoxyphenyl  335                                             2-methylpyrid-3-yloxy                                                                        thien-2-yl       311                                             2-methylpyrid-3-yloxy                                                                        2-bromophenyl    384                                             2-methylpyrid-3-yloxy                                                                        4-bromophenyl    384                                             2-methylpyrid-3-yloxy                                                                        4-fluoro-3-      391                                                           (trifluoromethyl)phenyl                                          2-methylpyrid-3-yloxy                                                                        3-(trifluoromethoxy)phenyl                                                                      389                                             2-methylpyrid-3-yloxy                                                                        9-fluorenon-4-yl 407                                             2-methylpyrid-3-yloxy                                                                        isoxazol-5-yl    296                                             2-methylpyrid-3-yloxy                                                                        benzofuroxan-5-yl                                                                               363                                             2-methylpyrid-3-yloxy                                                                        2-chloropyrid-3-yl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        3,5-difluorophenyl                                                                              341                                             2-methylpyrid-3-yloxy                                                                        2-(4-            412                                                           methylphenoxy)pyridin-3-yl                                       2-methylpyrid-3-yloxy                                                                        pyridin-4-yl     306                                             2-methylpyrid-3-yloxy                                                                        anthraquinon-2-yl                                                                               435                                             2-methylpyrid-3-yloxy                                                                        2-iodophenyl     431                                             4-chloro-2,5- 3,4-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(trifluoromethyl)phenyl                                                                       421                                             dimethylphenoxy                                                                4-chloro-2,5- 2,4-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-2,5- 3-(trifluoromethyl)phenyl                                                                       421                                             dimethylphenoxy                                                                4-chloro-2,5- 2-naphthyl       403                                             dimethylphenoxy                                                                4-chloro-2,5- 2-methoxyphenyl  484                                             dimethylphenoxy                                                                4-chloro-2,5- 3,4,5-trimethylphenyl                                                                           443                                             dimethylphenoxy                                                                4-chloro-2,5- 3,4-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-2,5- 3-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-2,5- 3-pyridyl        354                                             dimethylphenoxy                                                                4-chloro-2,5- 2-ethoxynaphth-1-yl                                                                             447                                             dimethylphenoxy                                                                4-chloro-2,5- 2,3-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-2,5- 6-chloropyrid-3-yl                                                                              388                                             dimethylphenoxy                                                                4-chloro-2,5- 4-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-2,5- 2-fluoro-4-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-2,5- 3-bromothienyl   438                                             dimethylphenoxy                                                                4-chloro-2,5- 2-acetoxyphenyl  411                                             dimethylphenoxy                                                                4-chloro-2,5- 5-methylisoxazol-3-yl                                                                           358                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(phenylthio)pyrid-3-yl                                                                        462                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-2,5- 1-phenyl-5-propylpyrazin-                                                                       461                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-2,5- 2-ethoxyphenyl   397                                             dimethylphenoxy                                                                4-chloro-2,5- 3-chlorothien-2-yl                                                                              393                                             dimethylphenoxy                                                                4-chloro-2,5- 1-(2-(2-methyl)propyl)-3-                                                                       413                                             dimethylphenoxy                                                                              methylpyrazol-5-yl                                               4-chloro-2,5- 3,5-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(propylthio)pyridin-3-yl                                                                      428                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(ethylthio)pyridin-3-yl                                                                       414                                             dimethylphenoxy                                                                4-chloro-2,5- 3-bromopyridin-5-yl                                                                             433                                             dimethylphenoxy                                                                4-chloro-2,5- 4-methyl-1,2,3-thiadiazol-                                                                      375                                             dimethylphenoxy                                                                              5-yl                                                             4-chloro-2,5- 1-methyl-3-(2-(2-                                                                               413                                             dimethylphenoxy                                                                              methyl)propyl)pyrazol-5-yl                                       4-chloro-2,5- 3-chlorobenzo[b]thiophen-                                                                       443                                             dimethylphenoxy                                                                              2-yl                                                             4-chloro-2,5- 4-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-2,5- 4-methyl-2-phenyl-1,2,3-                                                                        434                                             dimethylphenoxy                                                                              triazol-5-yl                                                     4-chloro-2,5- benzo[b]thiophen-2-yl                                                                           409                                             dimethylphenoxy                                                                4-chloro-2,5- 3,4-dimethylphenyl                                                                              381                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(phenoxy)pyridin-3-yl                                                                         446                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(methylthio)pyridin-3-yl                                                                      400                                             dimethylphenoxy                                                                4-chloro-2,5- 5-methyl-3-phenylisoxazol-                                                                      434                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-2,5- 4-chloro-1,3-dimethyl                                                                           456                                             dimethylphenoxy                                                                              pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-2,5- 2-chloro-6-methylpyridin-                                                                       402                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-2,5- 3,5-dimethylisoxazol-4-yl                                                                       372                                             dimethylphenoxy                                                                4-chloro-2,5- 1-naphthyl       403                                             dimethylphenoxy                                                                4-chloro-2,5- 2-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-2,5- 4-propylphenyl   395                                             dimethylphenoxy                                                                4-chloro-2,5- 3-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-2,5- 2,6-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-2,5- 2-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-2,5- 3-(chloromethyl)phenyl                                                                          401                                             dimethylphenoxy                                                                4-chloro-2,5- 4-(2-(2-         409                                             dimethylphenoxy                                                                              methyl)propyl)phenyl                                             4-chloro-2,5- 3-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-2,5- 3,5-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-2,5- 2,6-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-2,5- 2,4-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-2,5- 4-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-2,5- 4-butylphenyl    409                                             dimethylphenoxy                                                                4-chloro-2,5- 2-methylphenyl   367                                             dimethylphenoxy                                                                4-chloro-2,5- phenyl           353                                             dimethylphenoxy                                                                4-chloro-2,5- 4-ethylphenyl    381                                             dimethylphenoxy                                                                4-chloro-2,5- 2,3-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-2,5- 2,6-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-2,5- 3,4-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-2,5- 2,5-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-2,5- 4-ethoxyphenyl   397                                             dimethylphenoxy                                                                4-chloro-2,5- 2,4,6-trichlorophenyl                                                                           456                                             dimethylphenoxy                                                                4-chloro-2,5- 3-methylphenyl   367                                             dimethylphenoxy                                                                4-chloro-2,5- 2-fluoro-5-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-2,5- 3-methoxyphenyl  383                                             dimethylphenoxy                                                                4-chloro-2,5- 2-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-2,5- 4-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-2,5- 4-fluoro-3-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-2,5- 3-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-2,5- 9-fluorenon-4-yl 455                                             dimethylphenoxy                                                                4-chloro-2,5- isoxazol-5-yl    344                                             dimethylphenoxy                                                                4-chloro-2,5- benzofuroxan-5-yl                                                                               411                                             dimethylphenoxy                                                                4-chloro-2,5- 2-chloropyrid-3-yl                                                                              388                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(4-            460                                             dimethylphenoxy                                                                              methylphenoxy)pyridin-3-yl                                       4-chloro-2,5- pyridin-4-yl     354                                             dimethylphenoxy                                                                4-chloro-2,5- anthraquinon-2-yl                                                                               483                                             dimethylphenoxy                                                                4-chloro-2,5- 2-iodophenyl     479                                             dimethylphenoxy                                                                4-chloro-2,5- 4-pentylphenyl   423                                             dimethylphenoxy                                                                4-chloro-2,5- 2-(4-chlorophenylthio)                                                                          496                                             dimethylphenoxy                                                                              pyridin-3-yl                                                     4-chloro-2,5- 2,6-dimethylphenyl                                                                              381                                             dimethylphenoxy                                                                4-chloro-2,5- 2,5-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-2,5- 2,5-dichloropyridin-3-yl                                                                        423                                             dimethylphenoxy                                                                4-chloro-2,5- 2-chloro-6-methoxypyridin-                                                                      418                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-2,5  2,3-dichloropyridin-5-yl                                                                        423                                             dimethylphenoxy                                                                4-chloro-2,5  1-naphthyl       417                                             dimethylphenoxy                                                                4-chloro-2,5- 2,4-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-2,5- 3,5-bis(trifluoromethyl)                                                                        489                                             dimethylphenoxy                                                                              phenyl                                                           4-chloro-2,5- 2-(4-            480                                             dimethylphenoxy                                                                              chlorophenoxy)pyridin-3-yl                                       4-chloro-2,5- pentafluorophenyl                                                                               443                                             dimethylphenoxy                                                                4-methoxyphenoxy                                                                             3,4-dimethoxyphenyl                                                                             380                                             4-methoxyphenoxy                                                                             2-(trifluoromethyl)phenyl                                                                       388                                             4-methoxyphenoxy                                                                             2,4-difluorophenyl                                                                              356                                             4-methoxyphenoxy                                                                             3-(trifluoromethyl)phenyl                                                                       388                                             4-methoxyphenoxy                                                                             2-naphthyl       370                                             4-methoxyphenoxy                                                                             2-methoxyphenyl  350                                             4-methoxyphenoxy                                                                             3,5-trimethylphenyl                                                                             410                                             4-methoxyphenoxy                                                                             3,4-dichlorophenyl                                                                              389                                             4-methoxyphenoxy                                                                             3-bromophenyl    399                                             4-methoxyphenoxy                                                                             3-pyridyl        321                                             4-methoxyphenoxy                                                                             2-ethoxynaphth-1-yl                                                                             414                                             4-methoxyphenoxy                                                                             2,3-dichlorophenyl                                                                              389                                             4-methoxyphenoxy                                                                             6-chloropyrid-3-yl                                                                              356                                             4-methoxyphenoxy                                                                             4-(trifluoromethoxy)phenyl                                                                      404                                             4-methoxyphenoxy                                                                             2-fluoro-4-      406                                                           (trifluoromethyl)phenyl                                          4-methoxyphenoxy                                                                             3-bromothienyl   405                                             4-methoxyphenoxy                                                                             2-acetoxyphenyl  378                                             4-methoxyphenoxy                                                                             5-methylisoxazol-3-yl                                                                           325                                             4-methoxyphenoxy                                                                             2-(phenylthio)pyrid-3-yl                                                                        429                                             4-methoxyphenoxy                                                                             2-(trifluoromethoxy)phenyl                                                                      404                                             4-methoxyphenoxy                                                                             1-phenyl-5-propylpyrazin-                                                                       428                                                           4-yl                                                             4-methoxyphenoxy                                                                             2-ethoxyphenyl   364                                             4-methoxyphenoxy                                                                             3-chlorothien-2-yl                                                                              361                                             4-methoxyphenoxy                                                                             1-(2-(2-methyl)propyl)-3-                                                                       380                                                           methylpyrazol-5-yl                                               4-methoxyphenoxy                                                                             3,5-dichlorophenyl                                                                              389                                             4-methoxyphenoxy                                                                             2-(propylthio)pyridin-3-yl                                                                      395                                             4-methoxyphenoxy                                                                             2-(ethylthio)pyridin-3-yl                                                                       381                                             4-methoxyphenoxy                                                                             3-bromopyridin-5-yl                                                                             400                                             4-methoxyphenoxy                                                                             4-methyl-1,2,3-thiadiazol-                                                                      342                                                           5-yl                                                             4-methoxyphenoxy                                                                             1-methyl-3-(2-(2-                                                                               380                                                           methyl)propyl)pyrazol-5-yl                                       4-methoxyphenoxy                                                                             3-chlorobenzo[b]thiophen-                                                                       411                                                           2-yl                                                             4-methoxyphenoxy                                                                             4-chlorophenyl   355                                             4-methoxyphenoxy                                                                             4-methyl-2-phenyl-1,2,3-                                                                        401                                                           triazol-5-yl                                                     4-methoxyphenoxy                                                                             benzo[b]thiophen-2-yl                                                                           376                                             4-methoxyphenoxy                                                                             3,4-dimethylphenyl                                                                              348                                             4-methoxyphenoxy                                                                             2-(phenoxy)pyridin-3-yl                                                                         413                                             4-methoxyphenoxy                                                                             2-(methylthio)pyridin-3-yl                                                                      367                                             4-methoxyphenoxy                                                                             5-methyl-3-phenylisoxazol-                                                                      401                                                           4-yl                                                             4-methoxyphenoxy                                                                             4-chloro-1,3-dimethyl                                                                           424                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-methoxyphenoxy                                                                             2-chloro-6-methylpyridin-                                                                       370                                                           4-yl                                                             4-methoxyphenoxy                                                                             3,5-dimethylisoxazol-4-yl                                                                       339                                             4-methoxyphenoxy                                                                             1-naphthyl       370                                             4-methoxyphenoxy                                                                             2-fluorophenyl   338                                             4-methoxyphenoxy                                                                             4-propylphenyl   362                                             4-methoxyphenoxy                                                                             3-fluorophenyl   338                                             4-methoxyphenoxy                                                                             2,6-difluorophenyl                                                                              356                                             4-methoxyphenoxy                                                                             2-chlorophenyl   355                                             4-methoxyphenoxy                                                                             3-(chloromethyl)phenyl                                                                          369                                             4-methoxyphenoxy                                                                             4-(2-(2-         376                                                           methyl)propyl)phenyl                                             4-methoxyphenoxy                                                                             3-chlorophenyl   355                                             4-methoxyphenoxy                                                                             3,5-dimethoxyphenyl                                                                             380                                             4-methoxyphenoxy                                                                             2,6-dichlorophenyl                                                                              389                                             4-methoxyphenoxy                                                                             2,4-dichlorophenyl                                                                              389                                             4-methoxyphenoxy                                                                             4-fluorophenyl   338                                             4-methoxyphenoxy                                                                             4-butylphenyl    376                                             4-methoxyphenoxy                                                                             2-methylphenyl   334                                             4-methoxyphenoxy                                                                             phenyl           320                                             4-methoxyphenoxy                                                                             4-ethylphenyl    348                                             4-methoxyphenoxy                                                                             2,3-difluorophenyl                                                                              356                                             4-methoxyphenoxy                                                                             2,6-dimethoxyphenyl                                                                             380                                             4-methoxyphenoxy                                                                             3,4-difluorophenyl                                                                              356                                             4-methoxyphenoxy                                                                             2,5-difluorophenyl                                                                              356                                             4-methoxyphenoxy                                                                             4-ethoxyphenyl   364                                             4-methoxyphenoxy                                                                             2,4,6-trichlorophenyl                                                                           424                                             4-methoxyphenoxy                                                                             3-methylphenyl   334                                             4-methoxyphenoxy                                                                             2-fluoro-5-      406                                                           (trifluoromethyl)phenyl                                          4-methoxyphenoxy                                                                             3-methoxyphenyl  350                                             4-methoxyphenoxy                                                                             2-bromophenyl    399                                             4-methoxyphenoxy                                                                             4-bromophenyl    399                                             4-methoxyphenoxy                                                                             4-fluoro-3-      406                                                           (trifluoromethyl)phenyl                                          4-methoxyphenoxy                                                                             3-(trifluoromethoxy)phenyl                                                                      404                                             4-methoxyphenoxy                                                                             9-fluorenon-4-yl 422                                             4-methoxyphenoxy                                                                             isoxazol-5-yl    311                                             4-methoxyphenoxy                                                                             benzofuroxan-5-yl                                                                               378                                             4-methoxyphenoxy                                                                             2-chloropyrid-3-yl                                                                              356                                             4-methoxyphenoxy                                                                             2-(4-            427                                                           methylphenoxy)pyridin-3-yl                                       4-methoxyphenoxy                                                                             pyridin-4-yl     321                                             4-methoxyphenoxy                                                                             anthraquinon-2-yl                                                                               450                                             4-methoxyphenoxy                                                                             2-iodophenyl     446                                             4-methoxyphenoxy                                                                             4-pentylphenyl   390                                             4-methoxyphenoxy                                                                             2-(4-chlorophenylthio)                                                                          464                                                           pyridin-3-yl                                                     4-methoxyphenoxy                                                                             2,6-dimethylphenyl                                                                              348                                             4-methoxyphenoxy                                                                             2,5-dimethoxyphenyl                                                                             380                                             4-methoxyphenoxy                                                                             2,5-dichloropyridin-3-yl                                                                        390                                             4-methoxyphenoxy                                                                             2-chloro-6-methoxypyridin-                                                                      386                                                           4-yl                                                             4-methoxyphenoxy                                                                             2,3-dichloropyridin-5-yl                                                                        390                                             4-methoxyphenoxy                                                                             1-naphthyl       384                                             4-methoxyphenoxy                                                                             2,4-dimethoxyphenyl                                                                             380                                             4-methoxyphenoxy                                                                             3,5-bis(trifluoromethyl)                                                                        456                                                           phenyl                                                           4-methoxyphenoxy                                                                             2-(4-            448                                                           chlorophenoxy)pyridin-3-yl                                       4-methoxyphenoxy                                                                             pentafluorophenyl                                                                               410                                             2-(2-propoxy)phenoxy                                                                         3,4-dimethoxyphenyl                                                                             408                                             2-(2-propoxy)phenoxy                                                                         2-(trifluoromethyl)phenyl                                                                       416                                             2-(2-propoxy)phenoxy                                                                         2,4-difluorophenyl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         3-(trifluoromethyl)phenyl                                                                       416                                             2-(2-propoxy)phenoxy                                                                         2-naphthyl       398                                             2-(2-propoxy)phenoxy                                                                         2-methoxyphenyl  378                                             2-(2-propoxy)phenoxy                                                                         3,4,5-trimethylphenyl                                                                           438                                             2-(2-propoxy)phenoxy                                                                         3,4-dichlorophenyl                                                                              417                                             2-(2-propoxy)phenoxy                                                                         3-bromophenyl    427                                             2-(2-propoxy)phenoxy                                                                         3-pyridyl        349                                             2-(2-propoxy)phenoxy                                                                         2-ethoxynaphth-1-yl                                                                             442                                             2-(2-propoxy)phenoxy                                                                         2,3-dichlorophenyl                                                                              417                                             2-(2-propoxy)phenoxy                                                                         6-chloropyrid-3-yl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         4-(trifluoromethoxy)phenyl                                                                      432                                             2-(2-propoxy)phenoxy                                                                         2-fluoro-4-      434                                                           (trifluoromethyl)phenyl                                          2-(2-propoxy)phenoxy                                                                         3-bromothienyl   433                                             2-(2-propoxy)phenoxy                                                                         2-acetoxyphenyl  406                                             2-(2-propoxy)phenoxy                                                                         5-methylisoxazol-3-yl                                                                           353                                             2-(2-propoxy)phenoxy                                                                         2-(phenylthio)pyrid-3-yl                                                                        458                                             2-(2-propoxy)phenoxy                                                                         2-(trifluoromethoxy)phenyl                                                                      432                                             2-(2-propoxy)phenoxy                                                                         1-phenyl-5-propylpyrazin-                                                                       457                                                           4-yl                                                             2-(2-propoxy)phenoxy                                                                         2-ethoxyphenyl   392                                             2-(2-propoxy)phenoxy                                                                         3-chlorothien-2-yl                                                                              389                                             2-(2-propoxy)phenoxy                                                                         1-(2-(2-methyl)propyl)-3-                                                                       408                                                           methylpyrazol-5-yl                                               2-(2-propoxy)phenoxy                                                                         3,5-dichlorophenyl                                                                              417                                             2-(2-propoxy)phenoxy                                                                         2-(propylthio)pyridin-3-yl                                                                      423                                             2-(2-propoxy)phenoxy                                                                         2-(ethylthio)pyridin-3-yl                                                                       409                                             2-(2-propoxy)phenoxy                                                                         3-bromopyridin-5-yl                                                                             428                                             2-(2-propoxy)phenoxy                                                                         4-methyl-1,2,3-thiadiazol-                                                                      370                                                           5-yl                                                             2-(2-propoxy)phenoxy                                                                         1-methyl-3-(2-(2-                                                                               408                                                           methyl)propyl)pyrazol-5-yl                                       2-(2-propoxy)phenoxy                                                                         3-chlorobenzo[b]thiophen-                                                                       439                                                           2-yl                                                             2-(2-propoxy)phenoxy                                                                         4-chlorophenyl   383                                             2-(2-propoxy)phenoxy                                                                         4-methyl-2-phenyl-1,2,3-                                                                        429                                                           triazol-5-yl                                                     2-(2-propoxy)phenoxy                                                                         benzo[b]thiophen-2-yl                                                                           404                                             2-(2-propoxy)phenoxy                                                                         3,4-dimethylphenyl                                                                              376                                             2-(2-propoxy)phenoxy                                                                         2-(phenoxy)pyridin-3-yl                                                                         441                                             2-(2-propoxy)phenoxy                                                                         2-(methylthio)pyridin-3-yl                                                                      395                                             2-(2-propoxy)phenoxy                                                                         5-methyl-3-phenylisoxazol-                                                                      429                                                           4-yl                                                             2-(2-propoxy)phenoxy                                                                         4-chloro-1,3-dimethyl                                                                           452                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2-(2-propoxy)phenoxy                                                                         2-chloro-6-methylpyridin-                                                                       398                                                           4-yl                                                             2-(2-propoxy)phenoxy                                                                         3,5-dimethylisoxazol-4-yl                                                                       367                                             2-(2-propoxy)phenoxy                                                                         1-naphthyl       398                                             2-(2-propoxy)phenoxy                                                                         2-fluorophenyl   366                                             2-(2-propoxy)phenoxy                                                                         4-propylphenyl   390                                             2-(2-propoxy)phenoxy                                                                         3-fluorophenyl   366                                             2-(2-propoxy)phenoxy                                                                         2,6-difluorophenyl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         2-chlorophenyl   383                                             2-(2-propoxy)phenoxy                                                                         3-(chloromethyl)phenyl                                                                          397                                             2-(2-propoxy)phenoxy                                                                         4-(2-(2-         404                                                           methyl)propyl)phenyl                                             2-(2-propoxy)phenoxy                                                                         3-chlorophenyl   383                                             2-(2-propoxy)phenoxy                                                                         3,5-dimethoxyphenyl                                                                             408                                             2-(2-propoxy)phenoxy                                                                         2,6-dichlorophenyl                                                                              417                                             2-(2-propoxy)phenoxy                                                                         2,4-dichlorophenyl                                                                              417                                             2-(2-propoxy)phenoxy                                                                         4-fluorophenyl   366                                             2-(2-propoxy)phenoxy                                                                         4-butylphenyl    404                                             2-(2-propoxy)phenoxy                                                                         2-methylphenyl   362                                             2-(2-propoxy)phenoxy                                                                         phenyl           348                                             2-(2-propoxy)phenoxy                                                                         4-ethylphenyl    376                                             2-(2-propoxy)phenoxy                                                                         2,3-difluorophenyl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         2,6-dimethoxyphenyl                                                                             408                                             2-(2-propoxy)phenoxy                                                                         3,4-difluorophenyl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         2,5-difluorophenyl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         4-ethoxyphenyl   392                                             2-(2-propoxy)phenoxy                                                                         2,4,6-trichlorophenyl                                                                           452                                             2-(2-propoxy)phenoxy                                                                         3-methylphenyl   362                                             2-(2-propoxy)phenoxy                                                                         2-fluoro-5-      434                                                           (trifluoromethyl)phenyl                                          2-(2-propoxy)phenoxy                                                                         3-methoxyphenyl  378                                             2-(2-propoxy)phenoxy                                                                         2-bromophenyl    427                                             2-(2-propoxy)phenoxy                                                                         4-bromophenyl    427                                             2-(2-propoxy)phenoxy                                                                         4-fluoro-3-      434                                                           (trifluoromethyl)phenyl                                          2-(2-propoxy)phenoxy                                                                         3-(trifluoromethoxy)phenyl                                                                      432                                             2-(2-propoxy)phenoxy                                                                         9-fluorenon-4-yl 450                                             2-(2-propoxy)phenoxy                                                                         isoxazol-5-yl    339                                             2-(2-propoxy)phenoxy                                                                         benzofuroxan-5-yl                                                                               406                                             2-(2-propoxy)phenoxy                                                                         2-chloropyrid-3-yl                                                                              384                                             2-(2-propoxy)phenoxy                                                                         2-(4-            455                                                           methylphenoxy)pyridin-3-yl                                       2-(2-propoxy)phenoxy                                                                         pyridin-4-yl     349                                             2-(2-propoxy)phenoxy                                                                         anthraquinon-2-yl                                                                               478                                             2-(2-propoxy)phenoxy                                                                         2-iodophenyl     474                                             2-(2-propoxy)phenoxy                                                                         4-pentylphenyl   419                                             2-(2-propoxy)phenoxy                                                                         2-(4-chlorophenylthio)                                                                          492                                                           pyridin-3-yl                                                     2-(2-propoxy)phenoxy                                                                         2,6-dimethylphenyl                                                                              376                                             2-(2-propoxy)phenoxy                                                                         2,5-dimethoxyphenyl                                                                             408                                             2-(2-propoxy)phenoxy                                                                         2,5-dichloropyridin-3-yl                                                                        418                                             2-(2-propoxy)phenoxy                                                                         2-chloro-6-methoxypyridin-                                                                      414                                                           4-yl                                                             2-(2-propoxy)phenoxy                                                                         2,3-dichloropyridin-5-yl                                                                        418                                             2-(2-propoxy)phenoxy                                                                         1-naphthyl       412                                             2-(2-propoxy)phenoxy                                                                         2,4-dimethoxyphenyl                                                                             408                                             2-(2-propoxy)phenoxy                                                                         3,5-bis(trifluoromethyl)                                                                        484                                                           phenyl                                                           2-(2-propoxy)phenoxy                                                                         2-(4-            476                                                           chlorophenoxy)pyridin-3-yl                                       2-(2-propoxy)phenoxy                                                                         pentafluorophenyl                                                                               438                                             4-fluorophenoxy                                                                              3,4-dimethoxyphenyl                                                                             368                                             4-fluorophenoxy                                                                              2-(trifluoromethyl)phenyl                                                                       376                                             4-fluorophenoxy                                                                              2,4-difluorophenyl                                                                              344                                             4-fluorophenoxy                                                                              3-(trifluoromethyl)phenyl                                                                       376                                             4-fluorophenoxy                                                                              2-naphthyl       358                                             4-fluorophenoxy                                                                              2-methoxyphenyl  338                                             4-fluorophenoxy                                                                              3,4,5-trimethylphenyl                                                                           398                                             4-fluorophenoxy                                                                              3,4-dichlorophenyl                                                                              377                                             4-fluorophenoxy                                                                              3-bromophenyl    387                                             4-fluorophenoxy                                                                              3-pyridyl        309                                             4-fluorophenoxy                                                                              2-ethoxynaphth-1-yl                                                                             402                                             4-fluorophenoxy                                                                              2,3-dichlorophenyl                                                                              377                                             4-fluorophenoxy                                                                              6-chloropyrid-3-yl                                                                              344                                             4-fluorophenoxy                                                                              4-(trifluoromethoxy)phenyl                                                                      392                                             4-fluorophenoxy                                                                              2-fluoro-4-      394                                                           (trifluoromethyl)phenyl                                          4-fluorophenoxy                                                                              3-bromothienyl   393                                             4-fluorophenoxy                                                                              2-acetoxyphenyl  366                                             4-fluorophenoxy                                                                              5-methylisoxazol-3-yl                                                                           313                                             4-fluorophenoxy                                                                              2-(phenylthio)pyrid-3-yl                                                                        417                                             4-fluorophenoxy                                                                              2-(trifluoromethoxy)phenyl                                                                      392                                             4-fluorophenoxy                                                                              1-phenyl-5-propylpyrazin-                                                                       416                                                           4-yl                                                             4-fluorophenoxy                                                                              2-ethoxyphenyl   352                                             4-fluorophenoxy                                                                              3-chlorothien-2-yl                                                                              349                                             4-fluorophenoxy                                                                              1-(2-(2-methyl)propyl)-3-                                                                       368                                                           methylpyrazol-5-yl                                               4-fluorophenoxy                                                                              3,5-dichlorophenyl                                                                              377                                             4-fluorophenoxy                                                                              2-(propylthio)pyridin-3-yl                                                                      383                                             4-fluorophenoxy                                                                              2-(ethylthio)pyridin-3-yl                                                                       369                                             4-fluorophenoxy                                                                              3-bromopyridin-5-yl                                                                             388                                             4-fluorophenoxy                                                                              4-methyl-1,2,3-thiadiazol-                                                                      330                                                           5-yl                                                             4-fluorophenoxy                                                                              1-methyl-3-(2-(2-                                                                               368                                                           methyl)propyl)pyrazol-5-yl                                       4-fluorophenoxy                                                                              3-chlorobenzo[b]thiophen-                                                                       399                                                           2-yl                                                             4-fluorophenoxy                                                                              4-chlorophenyl   343                                             4-fluorophenoxy                                                                              4-methyl-2-phenyl-1,2,3-                                                                        389                                                           triazol-5-yl                                                     4-fluorophenoxy                                                                              benzo[b]thiophen-2-yl                                                                           364                                             4-fluorophenoxy                                                                              3,4-dimethylphenyl                                                                              336                                             4-fluorophenoxy                                                                              2-(phenoxy)pyridin-3-yl                                                                         401                                             4-fluorophenoxy                                                                              2-(methylthio)pyridin-3-yl                                                                      355                                             4-fluorophenoxy                                                                              5-methyl-3-phenylisoxazol-                                                                      389                                                           4-yl                                                             4-fluorophenoxy                                                                              4-chloro-1,3-dimethyl                                                                           412                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-fluorophenoxy                                                                              2-chloro-6-methylpyridin-                                                                       358                                                           4-yl                                                             4-fluorophenoxy                                                                              3,5-dimethylisoxazol-4-yl                                                                       327                                             4-fluorophenoxy                                                                              1-naphthyl       358                                             4-fluorophenoxy                                                                              2-fluorophenyl   326                                             4-fluorophenoxy                                                                              4-propylphenyl   350                                             4-fluorophenoxy                                                                              3-fluorophenyl   326                                             4-fluorophenoxy                                                                              2,6-difluorophenyl                                                                              344                                             4-fluorophenoxy                                                                              2-chlorophenyl   343                                             4-fluorophenoxy                                                                              3-(chloromethyl)phenyl                                                                          357                                             4-fluorophenoxy                                                                              4-(2-(2-         364                                                           methyl)propyl)phenyl                                             4-fluorophenoxy                                                                              3-chlorophenyl   343                                             4-fluorophenoxy                                                                              3,5-dimethoxyphenyl                                                                             368                                             4-fluorophenoxy                                                                              2,6-dichlorophenyl                                                                              377                                             4-fluorophenoxy                                                                              2,4-dichlorophenyl                                                                              377                                             4-fluorophenoxy                                                                              4-fluorophenyl   326                                             4-fluorophenoxy                                                                              4-butylphenyl    364                                             4-fluorophenoxy                                                                              2-methylphenyl   322                                             4-fluorophenoxy                                                                              phenyl           308                                             4-fluorophenoxy                                                                              4-ethylphenyl    336                                             4-fluorophenoxy                                                                              2,3-difluorophenyl                                                                              344                                             4-fluorophenoxy                                                                              2,6-dimethoxyphenyl                                                                             368                                             4-fluorophenoxy                                                                              3,4-difluorophenyl                                                                              344                                             4-fluorophenoxy                                                                              2,5-difluorophenyl                                                                              344                                             4-fluorophenoxy                                                                              4-ethoxyphenyl   352                                             4-fluorophenoxy                                                                              2,4,6-trichlorophenyl                                                                           412                                             4-fluorophenoxy                                                                              3-methylphenyl   322                                             4-fluorophenoxy                                                                              2-fluoro-5-      394                                                           (trifluoromethyl)phenyl                                          4-fluorophenoxy                                                                              3-methoxyphenyl  338                                             4-fluorophenoxy                                                                              2-bromophenyl    387                                             4-fluorophenoxy                                                                              4-bromophenyl    387                                             4-fluorophenoxy                                                                              4-fluoro-3-      394                                                           (trifluoromethyl)phenyl                                          4-fluorophenoxy                                                                              3-(trifluoromethoxy)phenyl                                                                      392                                             4-fluorophenoxy                                                                              9-fluorenon-4-yl 410                                             4-fluorophenoxy                                                                              isoxazol-5-yl    299                                             4-fluorophenoxy                                                                              benzofuroxan-5-yl                                                                               366                                             4-fluorophenoxy                                                                              2-chloropyrid-3-yl                                                                              344                                             4-fluorophenoxy                                                                              2-(4-            415                                                           methylphenoxy)pyridin-3-yl                                       4-fluorophenoxy                                                                              pyridin-4-yl     309                                             4-fluorophenoxy                                                                              anthraquinon-2-yl                                                                               438                                             4-fluorophenoxy                                                                              2-iodophenyl     434                                             4-fluorophenoxy                                                                              4-pentylphenyl   378                                             4-fluorophenoxy                                                                              2-(4-chlorophenylthio)                                                                          452                                                           pyridin-3-yl                                                     4-fluorophenoxy                                                                              2,6-dimethylphenyl                                                                              336                                             4-fluorophenoxy                                                                              2,5-dimethoxyphenyl                                                                             368                                             4-fluorophenoxy                                                                              2,5-dichloropyridin-3-yl                                                                        378                                             4-fluorophenoxy                                                                              2-chloro-6-methoxypyridin-                                                                      374                                                           4-yl                                                             4-fluorophenoxy                                                                              2,3-dichloropyridin-5-yl                                                                        378                                             4-fluorophenoxy                                                                              1-naphthyl       372                                             4-fluorophenoxy                                                                              2,4-dimethoxyphenyl                                                                             368                                             4-fluorophenoxy                                                                              3,5-             444                                                           bis(trifluoromethyl)phenyl                                       4-fluorophenoxy                                                                              2-(4-            436                                                           chlorophenoxy)pyridin-3-yl                                       4-fluorophenoxy                                                                              pentafluorophenyl                                                                               398                                             4-chlorophenoxy                                                                              3,4-dimethoxyphenyl                                                                             385                                             4-chlorophenoxy                                                                              2-(trifluoromethyl)phenyl                                                                       393                                             4-chlorophenoxy                                                                              2,4-difluorophenyl                                                                              361                                             4-chlorophenoxy                                                                              3-(trifluoromethyl)phenyl                                                                       393                                             4-chlorophenoxy                                                                              2-naphthyl       375                                             4-chlorophenoxy                                                                              2-methoxyphenyl  355                                             4-chlorophenoxy                                                                              3,4,5-trimethylphenyl                                                                           415                                             4-chlorophenoxy                                                                              3,4-dichlorophenyl                                                                              394                                             4-chlorophenoxy                                                                              3-bromophenyl    404                                             4-chlorophenoxy                                                                              3-pyridyl        326                                             4-chlorophenoxy                                                                              2-ethoxynaphth-1-yl                                                                             419                                             4-chlorophenoxy                                                                              2,3-dichlorophenyl                                                                              394                                             4-chlorophenoxy                                                                              6-chloropyrid-3-yl                                                                              360                                             4-chlorophenoxy                                                                              4-(trifluoromethoxy)phenyl                                                                      409                                             4-chlorophenoxy                                                                              2-fluoro-4-      411                                                           (trifluoromethyl)phenyl                                          4-chlorophenoxy                                                                              3-bromothienyl   410                                             4-chlorophenoxy                                                                              2-acetoxyphenyl  383                                             4-chlorophenoxy                                                                              5-methylisoxazol-3-yl                                                                           330                                             4-chlorophenoxy                                                                              2-(phenylthio)pyrid-3-yl                                                                        434                                             4-chlorophenoxy                                                                              2-(trifluoromethoxy)phenyl                                                                      409                                             4-chlorophenoxy                                                                              1-phenyl-5-propylpyrazin-                                                                       433                                                           4-yl                                                             4-chlorophenoxy                                                                              2-ethoxyphenyl   369                                             4-chlorophenoxy                                                                              3-chlorothien-2-yl                                                                              365                                             4-chlorophenoxy                                                                              1-(2-(2-methyl)propyl)-3-                                                                       385                                                           methylpyrazol-5-yl                                               4-chlorophenoxy                                                                              3,5-dichlorophenyl                                                                              394                                             4-chlorophenoxy                                                                              2-(propylthio)pyridin-3-yl                                                                      400                                             4-chlorophenoxy                                                                              2-(ethylthio)pyridin-3-yl                                                                       386                                             4-chlorophenoxy                                                                              3-bromopyridin-5-yl                                                                             405                                             4-chlorophenoxy                                                                              4-methyl-1,2,3-thiadiazol-                                                                      347                                                           5-yl                                                             4-chlorophenoxy                                                                              1-methyl-3-(2-(2-                                                                               385                                                           methyl)propyl)pyrazol-5-yl                                       4-chlorophenoxy                                                                              3-chlorobenzo[b]thiophen-                                                                       415                                                           2-yl                                                             4-chlorophenoxy                                                                              4-chlorophenyl   359                                             4-chlorophenoxy                                                                              4-methyl-2-phenyl-1,2,3-                                                                        406                                                           triazol-5-yl                                                     4-chlorophenoxy                                                                              benzo[b]thiophen-2-yl                                                                           381                                             4-chlorophenoxy                                                                              3,4-dimethylphenyl                                                                              353                                             4-chlorophenoxy                                                                              2-(phenoxy)pyridin-3-yl                                                                         418                                             4-chlorophenoxy                                                                              2-(methylthio)pyridin-3-yl                                                                      372                                             4-chlorophenoxy                                                                              5-methyl-3-phenylisoxazol-                                                                      406                                                           4-yl                                                             4-chlorophenoxy                                                                              4-chloro-1,3-dimethyl                                                                           428                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chlorophenoxy                                                                              2-chloro-6-methylpyridin-                                                                       374                                                           4-yl                                                             4-chlorophenoxy                                                                              3,5-dimethylisoxazol-4-yl                                                                       344                                             4-chlorophenoxy                                                                              1-naphthyl       375                                             4-chlorophenoxy                                                                              2-fluorophenyl   343                                             4-chlorophenoxy                                                                              4-propylphenyl   367                                             4-chlorophenoxy                                                                              3-fluorophenyl   343                                             4-chlorophenoxy                                                                              2,6-difluorophenyl                                                                              361                                             4-chlorophenoxy                                                                              2-chlorophenyl   359                                             4-chlorophenoxy                                                                              3-(chloromethyl)phenyl                                                                          373                                             4-chlorophenoxy                                                                              4-(2-(2-         381                                                           methyl)propyl)phenyl                                             4-chlorophenoxy                                                                              3-chlorophenyl   359                                             4-chlorophenoxy                                                                              3,5-dimethoxyphenyl                                                                             385                                             4-chlorophenoxy                                                                              2,6-dichlorophenyl                                                                              394                                             4-chlorophenoxy                                                                              2,4-dichlorophenyl                                                                              394                                             4-chlorophenoxy                                                                              4-fluorophenyl   343                                             4-chlorophenoxy                                                                              4-butylphenyl    381                                             4-chlorophenoxy                                                                              2-methylphenyl   339                                             4-chlorophenoxy                                                                              phenyl           325                                             4-chlorophenoxy                                                                              4-ethylphenyl    353                                             4-chlorophenoxy                                                                              2,3-difluorophenyl                                                                              361                                             4-chlorophenoxy                                                                              2,6-dimethoxyphenyl                                                                             385                                             4-chlorophenoxy                                                                              3,4-difluorophenyl                                                                              361                                             4-chlorophenoxy                                                                              2,5-difluorophenyl                                                                              361                                             4-chlorophenoxy                                                                              4-ethoxyphenyl   369                                             4-chlorophenoxy                                                                              2,4,6-trichlorophenyl                                                                           428                                             4-chlorophenoxy                                                                              3-methylphenyl   339                                             4-chlorophenoxy                                                                              2-fluoro-5-      411                                                           (trifluoromethyl)phenyl                                          4-chlorophenoxy                                                                              3-methoxyphenyl  355                                             4-chlorophenoxy                                                                              2-bromophenyl    404                                             4-chlorophenoxy                                                                              4-bromophenyl    404                                             4-chlorophenoxy                                                                              4-fluoro-3-      411                                                           (trifluoromethyl)phenyl                                          4-chlorophenoxy                                                                              3-(trifluoromethoxy)phenyl                                                                      409                                             4-chlorophenoxy                                                                              9-fluorenon-4-yl 427                                             4-chlorophenoxy                                                                              isoxazol-5-yl    316                                             4-chlorophenoxy                                                                              benzofuroxan-5-yl                                                                               383                                             4-chlorophenoxy                                                                              2-chloropyrid-3-yl                                                                              360                                             4-chlorophenoxy                                                                              2-(4-            432                                                           methylphenoxy)pyridin-3-yl                                       4-chlorophenoxy                                                                              pyridin-4-yl     326                                             4-chlorophenoxy                                                                              anthraquinon-2-yl                                                                               455                                             4-chlorophenoxy                                                                              2-iodophenyl     451                                             4-chlorophenoxy                                                                              4-pentylphenyl   395                                             4-chlorophenoxy                                                                              2-(4-chlorophenylthio)                                                                          468                                                           pyridin-3-yl                                                     4-chlorophenoxy                                                                              2,6-dimethylphenyl                                                                              353                                             4-chlorophenoxy                                                                              2,5-dimethoxyphenyl                                                                             385                                             4-chlorophenoxy                                                                              2,5-dichloropyridin-3-yl                                                                        395                                             4-chlorophenoxy                                                                              2-chloro-6-methoxypyridin-                                                                      390                                                           4-yl                                                             4-chlorophenoxy                                                                              2,3-dichloropyridin-5-yl                                                                        395                                             4-chlorophenoxy                                                                              1-naphthyl       389                                             4-chlorophenoxy                                                                              2,4-dimethoxyphenyl                                                                             385                                             4-chlorophenoxy                                                                              3,5-             461                                                           bis(trifluoromethyl)phenyl                                       4-chlorophenoxy                                                                              2-(4-            452                                                           chlorophenoxy)pyridin-3-yl                                       4-chlorophenoxy                                                                              pentafluorophenyl                                                                               415                                             2,4-difluorophenoxy                                                                          3,4-dimethoxyphenyl                                                                             386                                             2,4-difluorophenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       394                                             2,4-difluorophenoxy                                                                          2,4-difluorophenyl                                                                              362                                             2,4-difluorophenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       394                                             2,4-difluorophenoxy                                                                          2-naphthyl       376                                             2,4-difluorophenoxy                                                                          2-methoxyphenyl  356                                             2,4-difluorophenoxy                                                                          3,4,5-trimethylphenyl                                                                           416                                             2,4-difluorophenoxy                                                                          3,4-dichlorophenyl                                                                              395                                             2,4-difluorophenoxy                                                                          3-bromophenyl    405                                             2,4-difluorophenoxy                                                                          3-pyridyl        327                                             2,4-difluorophenoxy                                                                          2-ethoxynaphth-1-yl                                                                             420                                             2,4-difluorophenoxy                                                                          2,3-dichlorophenyl                                                                              395                                             2,4-difluorophenoxy                                                                          6-chloropyrid-3-yl                                                                              362                                             2,4-difluorophenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      410                                             2,4-difluorophenoxy                                                                          2-fluoro-4-      412                                                           (trifluoromethyl)phenyl                                          2,4-difluorophenoxy                                                                          3-bromothienyl   411                                             2,4-difluorophenoxy                                                                          2-acetoxyphenyl  384                                             2,4-difluorophenoxy                                                                          5-methylisoxazol-3-yl                                                                           331                                             2,4-difluorophenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        435                                             2,4-difluorophenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      410                                             2,4-difluorophenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       434                                                           4-yl                                                             2,4-difluorophenoxy                                                                          2-ethoxyphenyl   370                                             2,4-difluorophenoxy                                                                          3-chlorothien-2-yl                                                                              367                                             2,4-difluorophenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       386                                                           methylpyrazol-5-yl                                               2,4-difluorophenoxy                                                                          3,5-dichlorophenyl                                                                              395                                             2,4-difluorophenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      401                                             2,4-difluorophenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       387                                             2,4-difluorophenoxy                                                                          3-bromopyridin-5-yl                                                                             406                                             2,4-difluorophenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      348                                                           5-yl                                                             2,4-difluorophenoxy                                                                          1-methyl-3-(2-(2-                                                                               386                                                           methyl)propyl)pyrazol-5-yl                                       2,4-difluorophenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       417                                                           2-yl                                                             2,4-difluorophenoxy                                                                          4-chlorophenyl   361                                             2,4-difluorophenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        407                                                           triazol-5-yl                                                     2,4-difluorophenoxy                                                                          benzo[b]thiophen-2-yl                                                                           382                                             2,4-difluorophenoxy                                                                          3,4-dimethylphenyl                                                                              354                                             2,4-difluorophenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         409                                             2,4-difluorophenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      373                                             2,4-difluorophenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      407                                                           4-yl                                                             2,4-difluorophenoxy                                                                          4-chloro-1,3-dimethyl                                                                           430                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2,4-difluorophenoxy                                                                          2-chloro-6-methylpyridin-                                                                       376                                                           4-yl                                                             2,4-difluorophenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       345                                             2,4-difluorophenoxy                                                                          1-naphthyl       376                                             2,4-difluorophenoxy                                                                          2-fluorophenyl   344                                             2,4-difluorophenoxy                                                                          4-propylphenyl   368                                             2,4-difluorophenoxy                                                                          3-fluorophenyl   344                                             2,4-difluorophenoxy                                                                          2,6-difluorophenyl                                                                              362                                             2,4-difluorophenoxy                                                                          2-chlorophenyl   361                                             2,4-difluorophenoxy                                                                          3-(chloromethyl)phenyl                                                                          375                                             2,4-difluorophenoxy                                                                          4-(2-(2-         382                                                           methyl)propyl)phenyl                                             2,4-difluorophenoxy                                                                          3-chlorophenyl   361                                             2,4-difluorophenoxy                                                                          3,5-dimethoxyphenyl                                                                             386                                             2,4-difluorophenoxy                                                                          2,6-dichlorophenyl                                                                              395                                             2,4-difluorophenoxy                                                                          2,4-dichlorophenyl                                                                              392                                             2,4-difluorophenoxy                                                                          4-fluorophenyl   344                                             2,4-difluorophenoxy                                                                          4-butylphenyl    382                                             2,4-difluorophenoxy                                                                          2-methylphenyl   340                                             2,4-difluorophenoxy                                                                          phenyl           326                                             2,4-difluorophenoxy                                                                          4-ethylphenyl    354                                             2,4-difluorophenoxy                                                                          2,3-difluorophenyl                                                                              362                                             2,4-difluorophenoxy                                                                          2,6-dimethoxyphenyl                                                                             386                                             2,4-difluorophenoxy                                                                          3,4-difluorophenyl                                                                              362                                             2,4-difluorophenoxy                                                                          2,5-difluorophenyl                                                                              362                                             2,4-difluorophenoxy                                                                          4-ethoxyphenyl   370                                             2,4-difluorophenoxy                                                                          2,4,6-trichlorophenyl                                                                           430                                             2,4-difluorophenoxy                                                                          3-methylphenyl   340                                             2,4-difluorophenoxy                                                                          2-fluoro-5-      412                                                           (trifluoromethyl)phenyl                                          2,4-difluorophenoxy                                                                          3-methoxyphenyl  356                                             2,4-difluorophenoxy                                                                          2-bromophenyl    405                                             2,4-difluorophenoxy                                                                          4-bromophenyl    405                                             2,4-difluorophenoxy                                                                          4-fluoro-3-      412                                                           (trifluoromethyl)phenyl                                          2,4-difluorophenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      410                                             2,4-difluorophenoxy                                                                          9-fluorenon-4-yl 428                                             2,4-difluorophenoxy                                                                          isoxazol-5-yl    317                                             2,4-difluorophenoxy                                                                          benzofuroxan-5-yl                                                                               384                                             2,4-difluorophenoxy                                                                          2-chloropyrid-3-yl                                                                              362                                             2,4-difluorophenoxy                                                                          2-(4-            433                                                           methylphenoxy)pyridin-3-yl                                       2,4-difluorophenoxy                                                                          pyridin-4-yl     327                                             2,4-difluorophenoxy                                                                          anthraquinon-2-yl                                                                               456                                             2,4-difluorophenoxy                                                                          2-iodophenyl     452                                             2,4-difluorophenoxy                                                                          4-pentylphenyl   396                                             2,4-difluorophenoxy                                                                          2-(4-chlorophenylthio)                                                                          470                                                           pyridin-3-yl                                                     2,4-difluorophenoxy                                                                          2,6-dimethylphenyl                                                                              354                                             2,4-difluorophenoxy                                                                          2,5-dimethoxyphenyl                                                                             386                                             2,4-difluorophenoxy                                                                          2,5-dichloropyridin-3-yl                                                                        396                                             2,4-difluorophenoxy                                                                          2-chloro-6-methoxypyridin-                                                                      392                                                           4-yl                                                             2,4-difluorophenoxy                                                                          2,3-dichloropyridin-5-yl                                                                        396                                             2,4-difluorophenoxy                                                                          1-naphthyl       390                                             2 ,4-difluorophenoxy                                                                         2,4-dimethoxyphenyl                                                                             386                                             2,4-difluorophenoxy                                                                          3,5-             462                                                           bis(trifluoromethyl)phenyl                                       2,4-difluorophenoxy                                                                          2-(4-            454                                                           chlorophenoxy)pyridin-3-yl                                       2,4-difluorophenoxy                                                                          pentafluorophenyl                                                                               416                                             4-thiomethylphenoxy                                                                          3,4-dimethoxyphenyl                                                                             396                                             4-thiomethylphenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       404                                             4-thiomethylphenoxy                                                                          2,4-difluorophenyl                                                                              372                                             4-thiomethylphenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       404                                             4-thiomethylphenoxy                                                                          2-naphthyl       386                                             4-thiomethylphenoxy                                                                          2-methoxyphenyl  366                                             4-thiomethylphenoxy                                                                          3,4,5,-trimethylphenyl                                                                          426                                             4-thiomethylphenoxy                                                                          3,4-dichlorophenyl                                                                              405                                             4-thiomethylphenoxy                                                                          3-bromophenyl    415                                             4-thiomethylphenoxy                                                                          3-pyridyl        337                                             4-thiomethylphenoxy                                                                          2-ethoxynaphth-1-yl                                                                             430                                             4-thiomethylphenoxy                                                                          2,3-dichlorophenyl                                                                              405                                             4-thiomethylphenoxy                                                                          6-chloropyrid-3-yl                                                                              372                                             4-thiomethylphenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      420                                             4-thiomethylphenoxy                                                                          2-fluoro-4-      422                                                           (trifluoromethyl)phenyl                                          4-thiomethylphenoxy                                                                          3-bromothienyl   421                                             4-thiomethylphenoxy                                                                          2-acetoxyphenyl  394                                             4-thiomethylphenoxy                                                                          5-methylisoxazol-3-yl                                                                           341                                             4-thiomethylphenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        446                                             4-thiomethylphenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      420                                             4-thiomethylphenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       445                                                           4-yl                                                             4-thiomethylphenoxy                                                                          2-ethoxyphenyl   380                                             4-thiomethylphenoxy                                                                          3-chlorothien-2-yl                                                                              377                                             4-thiomethylphenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       396                                                           methylpyrazol-5-yl                                               4-thiomethylphenoxy                                                                          3,5-dichlorophenyl                                                                              405                                             4-thiomethylphenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      412                                             4-thiomethylphenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       397                                             4-thiomethylphenoxy                                                                          3-bromopyridin-5-yl                                                                             416                                             4-thiomethylphenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      358                                                           5-yl                                                             4-thiomethylphenoxy                                                                          1-methyl-3-(2-(2-                                                                               396                                                           methyl)propyl)pyrazol-5-yl                                       4-thiomethylphenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       427                                                           2-yl                                                             4-thiomethylphenoxy                                                                          4-chlorophenyl   371                                             4-thiomethylphenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        417                                                           triazol-5-yl                                                     4-thiomethylphenoxy                                                                          benzo[b]thiophen-2-yl                                                                           392                                             4-thiomethylphenoxy                                                                          3,4-dimethylphenyl                                                                              364                                             4-thiomethylphenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         429                                             4-thiomethylphenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      383                                             4-thiomethylphenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      417                                                           4-yl                                                             4-thiomethylphenoxy                                                                          4-chloro-1,3-dimethyl                                                                           440                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-thiomethylphenoxy                                                                          2-chloro-6-methylpyridin-                                                                       386                                                           4-yl                                                             4-thiomethylphenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       355                                             4-thiomethylphenoxy                                                                          1-naphthyl       386                                             4-thiomethylphenoxy                                                                          2-fluorophenyl   354                                             4-thiomethylphenoxy                                                                          4-propylphenyl   378                                             4-thiomethylphenoxy                                                                          3-fluorophenyl   354                                             4-thiomethylphenoxy                                                                          2,6-difluorophenyl                                                                              372                                             4-thiomethylphenoxy                                                                          2-chlorophenyl   371                                             4-thiomethylphenoxy                                                                          3-(chloromethyl)phenyl                                                                          385                                             4-thiomethylphenoxy                                                                          4-(2-(2-         392                                                           methyl)propyl)phenyl                                             4-thiomethylphenoxy                                                                          3-chlorophenyl   371                                             4-thiomethylphenoxy                                                                          3,5-dimethoxyphenyl                                                                             396                                             4-thiomethylphenoxy                                                                          2,6-dichlorophenyl                                                                              405                                             4-thiomethylphenoxy                                                                          2,4-dichlorophenyl                                                                              405                                             4-thiomethylphenoxy                                                                          4-fluorophenyl   354                                             4-thiomethylphenoxy                                                                          4-butylphenyl    392                                             4-thiomethylphenoxy                                                                          2-methylphenyl   350                                             4-thiomethylphenoxy                                                                          phenyl           336                                             4-thiomethylphenoxy                                                                          4-ethylphenyl    364                                             4-thiomethylphenoxy                                                                          2,3-difluorophenyl                                                                              372                                             4-thiomethylphenoxy                                                                          2,6-dimethoxyphenyl                                                                             396                                             4-thiomethylphenoxy                                                                          3,4-difluorophenyl                                                                              372                                             4-thiomethylphenoxy                                                                          2,5-difluorophenyl                                                                              372                                             4-thiomethylphenoxy                                                                          4-ethoxyphenyl   380                                             4-thiomethylphenoxy                                                                          2,4,6-trichlorophenyl                                                                           440                                             4-thiomethylphenoxy                                                                          3-methylphenyl   350                                             4-thiomethylphenoxy                                                                          2-fluoro-5-      422                                                           (trifluoromethyl)phenyl                                          4-thiomethylphenoxy                                                                          3-methoxyphenyl  366                                             4-thiomethylphenoxy                                                                          2-bromophenyl    415                                             4-thiomethylphenoxy                                                                          4-bromophenyl    415                                             4-thiomethylphenoxy                                                                          4-fluoro-3-      422                                                           (trifluoromethyl)phenyl                                          4-thiomethylphenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      420                                             4-thiomethylphenoxy                                                                          9-fluorenon-4-yl 438                                             4-thiomethylphenoxy                                                                          isoxazol-5-yl    327                                             4-thiomethylphenoxy                                                                          benzofuroxan-5-yl                                                                               394                                             4-thiomethylphenoxy                                                                          2-chloropyrid-3-yl                                                                              372                                             4-thiomethylphenoxy                                                                          2-(4-            443                                                           methylphenoxy)pyridin-3-yl                                       4-thiomethylphenoxy                                                                          pyridin-4-yl     337                                             4-thiomethylphenoxy                                                                          anthraquinon-2-yl                                                                               466                                             4-thiomethylphenoxy                                                                          2-iodophenyl     462                                             4-thiomethylphenoxy                                                                          4-pentylphenyl   407                                             4-thiomethylphenoxy                                                                          2-(4-chlorophenylthio)                                                                          480                                                           pyridin-3-yl                                                     4-thiomethylphenoxy                                                                          2,6-dimethylphenyl                                                                              364                                             4-thiomethylphenoxy                                                                          2,5-dimethoxyphenyl                                                                             396                                             4-thiomethylphenoxy                                                                          2,5-dichloropyridin-3-yl                                                                        406                                             4-thiomethylphenoxy                                                                          2-chloro-6-methoxypyridin-                                                                      402                                                           4-yl                                                             4-thiomethylphenoxy                                                                          2,3-dichloropyridin-5-yl                                                                        406                                             4-thiomethylphenoxy                                                                          1-naphthyl       400                                             4-thiomethylphenoxy                                                                          2,4-dimethoxyphenyl                                                                             396                                             4-thiomethylphenoxy                                                                          3,5-             372                                                           bis(trifluoromethyl)phenyl                                       4-thiomethylphenoxy                                                                          2-(4-            464                                                           chlorophenoxy)pyridin-3-yl                                       4-thiomethylphenoxy                                                                          pentafluorophenyl                                                                               426                                             4-(2-(2-      3,4-dimethoxyphenyl                                                                             406                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(trifluoromethyl)phenyl                                                                       414                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,4-difluorophenyl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-(trifluoromethyl)phenyl                                                                       414                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-naphthyl       396                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-methoxyphenyl  376                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,4,5-trimethylphenyl                                                                           436                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,4-dichlorophenyl                                                                              415                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-bromophenyl    425                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-pyridyl        347                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-ethoxynaphth-1-yl                                                                             441                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,3-dichlorophenyl                                                                              415                                             methyl)propyl)phenoxy                                                          4-(2-(2-      6-chloropyrid-3-yl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-(trifluoromethoxy)phenyl                                                                      430                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-fluoro-4-      432                                             methyl)propyl)phenoxy                                                                        (trifluoromethyl)phenyl                                          4-(2-(2-      3-bromothienyl   431                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-acetoxyphenyl  404                                             methyl)propyl)phenoxy                                                          4-(2-(2-      5-methylisoxazol-3-yl                                                                           351                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(phenylthio)pyrid-3-yl                                                                        456                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(trifluoromethoxy)phenyl                                                                      430                                             methyl)propyl)phenoxy                                                          4-(2-(2-      1-phenyl-5-propylpyrazin-                                                                       455                                             methyl)propyl)phenoxy                                                                        4-yl                                                             4-(2-(2-      2-ethoxyphenyl   390                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-chlorothien-2-yl                                                                              387                                             methyl)propyl)phenoxy                                                          4-(2-(2-      1-(2-(2-methyl)propyl)-3-                                                                       406                                             methyl)propyl)phenoxy                                                                        methylpyrazol-5-yl                                               4-(2-(2-      3,5-dichlorophenyl                                                                              415                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(propylthio)pyridin-3-yl                                                                      422                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(ethylthio)pyridin-3-yl                                                                       407                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-bromopyridin-5-yl                                                                             426                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-methyl-1,2,3-thiadiazol-                                                                      368                                             methyl)propyl)phenoxy                                                                        5-yl                                                             4-(2-(2-      1-methyl-3-(2-(2-                                                                               406                                             methyl)propyl)phenoxy                                                                        methyl)propyl)pyrazol-5-yl                                       4-(2-(2-      3-chlorobenzo[b]thiophen-                                                                       437                                             methyl)propyl)phenoxy                                                                        2-yl                                                             4-(2-(2-      4-chlorophenyl   381                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-methyl-2-phenyl-1,2,3-                                                                        427                                             methyl)propyl)phenoxy                                                                        triazol-5-yl                                                     4-(2-(2-      benzo[b]thiophen-2-yl                                                                           402                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,4-dimethylphenyl                                                                              374                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(phenoxy)pyridin-3-yl                                                                         439                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(methylthio)pyridin-3-yl                                                                      393                                             methyl)propyl)phenoxy                                                          4-(2-(2-      5-methyl-3-phenylisoxazol-                                                                      427                                             methyl)propyl)phenoxy                                                                        4-yl                                                             4-(2-(2-      4-chloro-1,3-dimethyl                                                                           450                                             methyl)propyl)phenoxy                                                                        pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-(2-(2-      2-chloro-6-methylpyridin-                                                                       396                                             methyl)propyl)phenoxy                                                                        4-yl                                                             4-(2-(2-      3,5-dimethylisoxazol-4-yl                                                                       365                                             methyl)propyl)phenoxy                                                          4-(2-(2-      1-naphthyl       396                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-fluorophenyl   364                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-propylphenyl   388                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-fluorophenyl   364                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,6-difluorophenyl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-chlorophenyl   381                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-(chloromethyl)phenyl                                                                          395                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-(2-(2-         402                                             methyl)propyl)phenoxy                                                                        methyl)propyl)phenyl                                             4-(2-(2-      3-chlorophenyl   381                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,5-dimethoxyphenyl                                                                             406                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,6-dichlorophenyl                                                                              415                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,4-dichlorophenyl                                                                              415                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-fluorophenyl   364                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-butylphenyl    402                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-methylphenyl   360                                             methyl)propyl)phenoxy                                                          4-(2-(2-      phenyl           346                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-ethylphenyl    374                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,3-difluorophenyl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,6-dimethoxyphenyl                                                                             406                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,4-difluorophenyl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,5-difluorophenyl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-ethoxyphenyl   390                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,4,6-trichlorophenyl                                                                           450                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3-methylphenyl   360                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-fluoro-5-      432                                             methyl)propyl)phenoxy                                                                        (trifluoromethyl)phenyl                                          4-(2-(2-      3-methoxyphenyl  376                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-bromophenyl    425                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-bromophenyl    425                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-fluoro-3-      432                                             methyl)propyl)phenoxy                                                                        (trifluoromethyl)phenyl                                          4-(2-(2-      3-(trifluoromethoxy)phenyl                                                                      430                                             methyl)propyl)phenoxy                                                          4-(2-(2-      9-fluorenon-4-yl 448                                             methyl)propyl)phenoxy                                                          4-(2-(2-      isoxazol-5-yl    338                                             methyl)propyl)phenoxy                                                          4-(2-(2-      benzofuroxan-5-yl                                                                               404                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-chloropyrid-3-yl                                                                              382                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(4-            454                                             methyl)propyl)phenoxy                                                                        methylphenoxy)pyridin-3-yl                                       4-(2-(2-      pyridin-4-yl     347                                             methyl)propyl)phenoxy                                                          4-(2-(2-      anthraquinon-2-yl                                                                               476                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-iodophenyl     472                                             methyl)propyl)phenoxy                                                          4-(2-(2-      4-pentylphenyl   417                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-(4-chlorophenylthio)                                                                          490                                             methyl)propyl)phenoxy                                                                        pyridin-3-yl                                                     4-(2-(2-      2,6-dimethylphenyl                                                                              374                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,5-dimethoxyphenyl                                                                             406                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,5-dichloropyridin-3-yl                                                                        416                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2-chloro-6-methoxypyridin-                                                                      412                                             methyl)propyl)phenoxy                                                                        4-yl                                                             4-(2-(2-      2,3-dichloropyridin-5-yl                                                                        416                                             methyl)propyl)phenoxy                                                          4-(2-(2-      1-naphthyl       410                                             methyl)propyl)phenoxy                                                          4-(2-(2-      2,4-dimethoxyphenyl                                                                             406                                             methyl)propyl)phenoxy                                                          4-(2-(2-      3,5-bis(trifluoromethyl)                                                                        482                                             methyl)propyl)phenoxy                                                                        phenyl                                                           4-(2-(2-      2-(4-            474                                             methyl)propyl)phenoxy                                                                        chlorophenoxy)pyridin-3-yl                                       4-(2-(2-      pentafluorophenyl                                                                               436                                             methyl)propyl)phenoxy                                                          2,3-dimethylphenoxy                                                                          3,4-dimethoxyphenyl                                                                             378                                             2,3-dimethylphenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       386                                             2,3-dimethylphenoxy                                                                          2,4-difluorophenyl                                                                              354                                             2,3-dimethylphenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       386                                             2,3-dimethylphenoxy                                                                          2-naphthyl       368                                             2,3-dimethylphenoxy                                                                          2-methoxyphenyl  348                                             2,3-dimethylphenoxy                                                                          3,4,5-trimethylphenyl                                                                           408                                             2,3-dimethylphenoxy                                                                          3,4-dichlorophenyl                                                                              387                                             2,3-dimethylphenoxy                                                                          3-bromophenyl    397                                             2,3-dimethylphenoxy                                                                          3-pyridyl        319                                             2,3-dimethylphenoxy                                                                          2-ethoxynaphth-1-yl                                                                             412                                             2,3-dimethylphenoxy                                                                          2,3-dichlorophenyl                                                                              387                                             2,3-dimethylphenoxy                                                                          6-chloropyrid-3-yl                                                                              354                                             2,3-dimethylphenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      402                                             2,3-dimethylphenoxy                                                                          2-fluoro-4-      404                                                           (trifluoromethyl)phenyl                                          2,3-dimethylphenoxy                                                                          3-bromothienyl   403                                             2,3-dimethylphenoxy                                                                          2-acetoxyphenyl  376                                             2,3-dimethylphenoxy                                                                          5-methylisoxazol-3-yl                                                                           323                                             2,3-dimethylphenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        427                                             2,3-dimethylphenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      402                                             2,3-dimethylphenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       426                                                           4-yl                                                             2,3-dimethylphenoxy                                                                          2-ethoxyphenyl   362                                             2,3-dimethylphenoxy                                                                          3-chlorothien-2-yl                                                                              359                                             2,3-dimethylphenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       378                                                           methylpyrazol-5-yl                                               2,3-dimethylphenoxy                                                                          3,5-dichlorophenyl                                                                              387                                             2,3-dimethylphenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      393                                             2,3-dimethylphenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       379                                             2,3-dimethylphenoxy                                                                          3-bromopyridin-5-yl                                                                             398                                             2,3-dimethylphenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      340                                                           5-yl                                                             2,3-dimethylphenoxy                                                                          1-methyl-3-(2-(2-                                                                               378                                                           methyl)propyl)pyrazol-5-yl                                       2,3-dimethylphenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       409                                                           2-yl                                                             2,3-dimethylphenoxy                                                                          4-chlorophenyl   353                                             2,3-dimethylphenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        399                                                           triazol-5-yl                                                     2,3-dimethylphenoxy                                                                          benzo[b]thiophen-2-yl                                                                           374                                             2,3-dimethylphenoxy                                                                          3,4-dimethylphenyl                                                                              346                                             2,3-dimethylphenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         411                                             2,3-dimethylphenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      365                                             2,3-dimethylphenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      399                                                           4-yl                                                             2,3-dimethylphenoxy                                                                          4-chloro-1,3-dimethyl                                                                           422                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2,3-dimethylphenoxy                                                                          2-chloro-6-methylpyridin-                                                                       368                                                           4-yl                                                             2,3-dimethylphenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       337                                             2,3-dimethylphenoxy                                                                          1-naphthyl       368                                             2,3-dimethylphenoxy                                                                          2-fluorophenyl   336                                             2,3-dimethylphenoxy                                                                          4-propylphenyl   360                                             2,3-dimethylphenoxy                                                                          3-fluorophenyl   336                                             2,3-dimethylphenoxy                                                                          2,6-difluorophenyl                                                                              354                                             2,3-dimethylphenoxy                                                                          2-chlorophenyl   353                                             2,3-dimethylphenoxy                                                                          3-(chloromethyl)phenyl                                                                          368                                             2,3-dimethylphenoxy                                                                          4-(2-(2-methyl)propyl)                                                                          374                                                           phenyl                                                           2,3-dimethylphenoxy                                                                          3-chlorophenyl   353                                             2,3-dimethylphenoxy                                                                          3,5-dimethoxyphenyl                                                                             378                                             2,3-dimethylphenoxy                                                                          2,6-dichlorophenyl                                                                              387                                             2,3-dimethylphenoxy                                                                          2,4-dichlorophenyl                                                                              387                                             2,3-dimethylphenoxy                                                                          4-fluorophenyl   336                                             2,3-dimethylphenoxy                                                                          4-butylphenyl    374                                             2,3-dimethylphenoxy                                                                          2-methylphenyl   332                                             2,3-dimethylphenoxy                                                                          phenyl           318                                             2,3-dimethylphenoxy                                                                          4-ethylphenyl    346                                             2,3-dimethylphenoxy                                                                          2,3-difluorophenyl                                                                              354                                             2,3-dimethylphenoxy                                                                          2,6-dimethoxyphenyl                                                                             378                                             2,3-dimethylphenoxy                                                                          3,4-difluorophenyl                                                                              354                                             2,3-dimethylphenoxy                                                                          2,5-difluorophenyl                                                                              354                                             2,3-dimethylphenoxy                                                                          4-ethoxyphenyl   362                                             2,3-dimethylphenoxy                                                                          2,4,6-trichlorophenyl                                                                           422                                             2,3-dimethylphenoxy                                                                          3-methylphenyl   332                                             2,3-dimethylphenoxy                                                                          2-fluoro-5-      404                                                           (trifluoromethyl)phenyl                                          2,3-dimethylphenoxy                                                                          3-methoxyphenyl  348                                             2,3-dimethylphenoxy                                                                          2-bromophenyl    397                                             2,3-dimethylphenoxy                                                                          4-bromophenyl    397                                             2,3-dimethylphenoxy                                                                          4-fluoro-3-      404                                                           (trifluoromethyl)phenyl                                          2,3-dimethylphenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      402                                             2,3-dimethylphenoxy                                                                          9-fluorenon-4-yl 420                                             2,3-dimethylphenoxy                                                                          isoxazol-5-yl    609                                             2,3-dimethylphenoxy                                                                          benzofuroxan-5-yl                                                                               376                                             2,3-dimethylphenoxy                                                                          2-chloropyrid-3-yl                                                                              354                                             2,3-dimethylphenoxy                                                                          2-(4-            425                                                           methylphenoxy)pyridin-3-yl                                       2,3-dimethylphenoxy                                                                          pyridin-4-yl     319                                             2,3-dimethylphenoxy                                                                          anthraquinon-2-yl                                                                               448                                             2,3-dimethylphenoxy                                                                          2-iodophenyl     444                                             2,3-dimethylphenoxy                                                                          4-pentylphenyl   388                                             2,3-dimethylphenoxy                                                                          2-(4-chlorophenylthio)                                                                          462                                                           pyridin-3-yl                                                     2,3-dimethylphenoxy                                                                          2,6-dimethylphenyl                                                                              346                                             2,3-dimethylphenoxy                                                                          2,5-dimethoxyphenyl                                                                             378                                             2,3-dimethylphenoxy                                                                          2,5-dichloropyridin-3-yl                                                                        388                                             2,3-dimethylphenoxy                                                                          2-chloro-6-methoxypyridin-                                                                      384                                                           4-yl                                                             2,3-dimethylphenoxy                                                                          2,3-dichloropyridin-5-yl                                                                        388                                             2,3-dimethylphenoxy                                                                          1-naphthyl       382                                             2,3-dimethylphenoxy                                                                          2,4-dimethoxyphenyl                                                                             378                                             2,3-dimethylphenoxy                                                                          3,5-bis(trifluoromethyl)                                                                        454                                                           phenyl                                                           2,3-dimethylphenoxy                                                                          2-(4-            446                                                           chlorophenoxy)pyridin-3-yl                                       2,3-dimethylphenoxy                                                                          pentafluorophenyl                                                                               408                                             3,5-(bis-2-   3,4-dimethoxyphenyl                                                                             434                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(trifluoromethyl)phenyl                                                                       442                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,4-difluorophenyl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-(trifluoromethyl)phenyl                                                                       442                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-naphthyl       425                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-methoxyphenyl  404                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,4,5-trimethylphenyl                                                                           465                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,4-dichlorophenyl                                                                              443                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-bromophenyl    453                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-pyridyl        375                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-ethoxynaphth-1-yl                                                                             469                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,3-dichlorophenyl                                                                              443                                             propyl)phenoxy                                                                 3,5-(bis-2-   6-chloropyrid-3-yl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-(trifluoromethoxy)phenyl                                                                      458                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-fluoro-4-      460                                             propyl)phenoxy                                                                               (trifluoromethyl)phenyl                                          3,5-(bis-2-   3-bromothienyl   459                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-acetoxyphenyl  432                                             propyl)phenoxy                                                                 3,5-(bis-2-   5-methylisoxazol-3-yl                                                                           379                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(phenylthio)pyrid-3-yl                                                                        484                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(trifluoromethoxy)phenyl                                                                      458                                             propyl)phenoxy                                                                 3,5-(bis-2-   1-phenyl-5-propylpyrazin-                                                                       483                                             propyl)phenoxy                                                                               4-yl                                                             3,5-(bis-2-   2-ethoxyphenyl   418                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-chlorothiophen-2-yl                                                                           415                                             propyl)phenoxy                                                                 3,5-(bis-2-   1-(2-(2-methyl)propyl)-3-                                                                       435                                             propyl)phenoxy                                                                               methylpyrazol-5-yl                                               3,5-(bis-2-   3,5-dichlorophenyl                                                                              443                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(propylthio)pyridin-3-yl                                                                      450                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(ethylthio)pyridin-3-yl                                                                       436                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-bromopyridin-5-yl                                                                             454                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-methyl-1,2,3-thiadiazol-                                                                      396                                             propyl)phenoxy                                                                               5-yl                                                             3,5-(bis-2-   1-methyl-3-(2-(2-                                                                               435                                             propyl)phenoxy                                                                               methyl)propyl)pyrazol-5-yl                                       3,5-(bis-2-   3-chlorobenzo[b]thiophen-                                                                       465                                             propyl)phenoxy                                                                               2-yl                                                             3,5-(bis-2-   4-chlorophenyl   409                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-methyl-2-phenyl-1,2,3-                                                                        456                                             propyl)phenoxy                                                                               triazol-5-yl                                                     3,5-(bis-2-   benzo[b]thiophen-2-yl                                                                           431                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,4-dimethylphenyl                                                                              402                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(phenoxy)pyridin-3-yl                                                                         468                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(methylthio)pyridin-3-yl                                                                      422                                             propyl)phenoxy                                                                 3,5-(bis-2-   5-methyl-3-phenylisoxazol-                                                                      456                                             propyl)phenoxy                                                                               4-yl                                                             3,5-(bis-2-   4-chloro-1,3-dimethyl                                                                           478                                             propyl)phenoxy                                                                               pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               3,5-(bis-2-   2-chloro-6-methylpyridin-                                                                       424                                             propyl)phenoxy                                                                               4-yl                                                             3,5-(bis-2-   3,5-dimethylisoxazol-4-yl                                                                       393                                             propyl)phenoxy                                                                 3,5-(bis-2-   1-naphthyl       425                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-fluorophenyl   392                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-propylphenyl   417                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-fluorophenyl   392                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,6-difluorophenyl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-chlorophenyl   409                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-(chloromethyl)phenyl                                                                          423                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-(2-(2-methyl)propyl)                                                                          431                                             propyl)phenoxy                                                                               phenyl                                                           3,5-(bis-2-   3-chlorophenyl   409                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,5-dimethoxyphenyl                                                                             434                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,6-dichlorophenyl                                                                              443                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,4-dichlorophenyl                                                                              443                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-fluorophenyl   392                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-butylphenyl    431                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-methylphenyl   388                                             propyl)phenoxy                                                                 3,5-(bis-2-   phenyl           374                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-ethylphenyl    402                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,3-difluorophenyl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,6-dimethoxyphenyl                                                                             434                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,4-difluorophenyl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,5-difluorophenyl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-ethoxyphenyl   418                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,4,6-trichlorophenyl                                                                           478                                             propyl)phenoxy                                                                 3,5-(bis-2-   3-methylphenyl   388                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-fluoro-5-      460                                             propyl)phenoxy                                                                               (trifluoromethyl)phenyl                                          3,5-(bis-2-   3-methoxyphenyl  404                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-bromophenyl    453                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-bromophenyl    453                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-fluoro-3-      460                                             propyl)phenoxy                                                                               (trifluoromethyl)phenyl                                          3,5-(bis-2-   3-(trifluoromethoxy)phenyl                                                                      458                                             propyl)phenoxy                                                                 3,5-(bis-2-   9-fluorenon-4-yl 477                                             propyl)phenoxy                                                                 3,5-(bis-2-   isoxazol-5-yl    365                                             propyl)phenoxy                                                                 3,5-(bis-2-   benzofuroxan-5-yl                                                                               432                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-chloropyrid-3-yl                                                                              410                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(4-            482                                             propyl)phenoxy                                                                               methylphenoxy)pyridin-3-yl                                       3,5-(bis-2-   pyridin-4-yl     375                                             propyl)phenoxy                                                                 3,5-(bis-2-   anthraquinon-2-yl                                                                               505                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-iodophenyl     500                                             propyl)phenoxy                                                                 3,5-(bis-2-   4-pentylphenyl   445                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-(4-chlorophenylthio)                                                                          518                                             propyl)phenoxy                                                                               pyridin-3-yl                                                     3,5-(bis-2-   2,6-dimethylphenyl                                                                              402                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,5-dimethoxyphenyl                                                                             434                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,5-dichloropyridin-3-yl                                                                        444                                             propyl)phenoxy                                                                 3,5-(bis-2-   2-chloro-6-methoxypyridin-                                                                      440                                             propyl)phenoxy                                                                               4-yl                                                             3,5-(bis-2-   2,3-dichloropyridin-5-yl                                                                        444                                             propyl)phenoxy                                                                 3,5-(bis-2-   1-naphthyl       439                                             propyl)phenoxy                                                                 3,5-(bis-2-   2,4-dimethoxyphenyl                                                                             434                                             propyl)phenoxy                                                                 3,5-(bis-2-   3,5-bis(trifluoromethyl)                                                                        510                                             propyl)phenoxy                                                                               phenyl                                                           3,5-(bis-2-   2-(4-            502                                             propyl)phenoxy                                                                               chlorophenoxy)pyridin-3-yl                                       3,5-(bis-2-   pentafluorophenyl                                                                               464                                             propyl)phenoxy                                                                 3-trifluoromethyl                                                                            3,4-dimethoxyphenyl                                                                             418                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(trifluoromethyl)phenyl                                                                       426                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,4-difluorophenyl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-(trifluoromethyl)phenyl                                                                       426                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-naphthyl       408                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-methoxyphenyl  388                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,4,5-trimethylphenyl                                                                           448                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,4-dichlorophenyl                                                                              427                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-bromophenyl    437                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-pyridyl        359                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-ethoxynaphth-1-yl                                                                             452                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,3-dichlorophenyl                                                                              427                                             phenoxy                                                                        3-trifluoromethyl                                                                            6-chloropyrid-3-yl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-(trifluoromethoxy)phenyl                                                                      442                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-fluoro-4-      444                                             phenoxy       (trifluoromethyl)phenyl                                          3-trifluoromethyl                                                                            3-bromothienyl   443                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-acetoxyphenyl  416                                             phenoxy                                                                        3-trifluoromethyl                                                                            5-methylisoxazol-3-yl                                                                           363                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(phenylthio)pyrid-3-yl                                                                        467                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(trifluoromethoxy)phenyl                                                                      442                                             phenoxy                                                                        3-trifluoromethyl                                                                            1-phenyl-5-propylpyrazin-                                                                       466                                             phenoxy       4-yl                                                             3-trifluoromethyl                                                                            2-ethoxyphenyl   402                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-chlorothien-2-yl                                                                              399                                             phenoxy                                                                        3-trifluoromethyl                                                                            1-(2-(2-methyl)propyl)-3-                                                                       418                                             phenoxy       methylpyrazol-5-yl                                               3-trifluoromethyl                                                                            3,5-dichlorophenyl                                                                              427                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(propylthio)pyridin-3-yl                                                                      433                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(ethylthio)pyridin-3-yl                                                                       419                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-bromopyridin-5-yl                                                                             438                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-methyl-1,2,3-thiadiazol-                                                                      380                                             phenoxy       5-yl                                                             3-trifluoromethyl                                                                            1-methyl-3-(2-(2-                                                                               418                                             phenoxy       methyl)propyl)pyrazol-5-yl                                       3-trifluoromethyl                                                                            3-chlorobenzo[b]thiophen-                                                                       449                                             phenoxy       2-yl                                                             3-trifluoromethyl                                                                            4-chlorophenyl   393                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-methyl-2-phenyl-1,2,3-                                                                        439                                             phenoxy       triazol-5-yl                                                     3-trifluoromethyl                                                                            benzo[b]thiophen-2-yl                                                                           414                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,4-dimethylphenyl                                                                              386                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(phenoxy)pyridin-3-yl                                                                         451                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(methylthio)pyridin-3-yl                                                                      405                                             phenoxy                                                                        3-trifluoromethyl                                                                            5-methyl-3-phenylisoxazol-                                                                      439                                             phenoxy       4-yl                                                             3-trifluoromethyl                                                                            4-chloro-1,3-dimethyl                                                                           462                                             phenoxy       pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               3-trifluoromethyl                                                                            2-chloro-6-methylpyridin-                                                                       408                                             phenoxy       4-yl                                                             3-trifluoromethyl                                                                            3,5-dimethylisoxazol-4-yl                                                                       377                                             phenoxy                                                                        3-trifluoromethyl                                                                            1-naphthyl       408                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-fluorophenyl   476                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-propylphenyl   400                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-fluorophenyl   376                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,6-difluorophenyl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-chlorophenyl   393                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-(chloromethyl)phenyl                                                                          407                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-(2-(2-methyl)propyl)                                                                          414                                             phenoxy       phenyl                                                           3-trifluoromethyl                                                                            3-chlorophenyl   393                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,5-dimethoxyphenyl                                                                             418                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,6-dichlorophenyl                                                                              427                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,4-dichlorophenyl                                                                              427                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-fluorophenyl   376                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-butylphenyl    414                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-methylphenyl   372                                             phenoxy                                                                        3-trifluoromethyl                                                                            phenyl           358                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-ethylphenyl    386                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,3-difluorophenyl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,6-dimethoxyphenyl                                                                             418                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,4-difluorophenyl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,5-difluorophenyl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-ethoxyphenyl   402                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,4,6-trichlorophenyl                                                                           462                                             phenoxy                                                                        3-trifluoromethyl                                                                            3-methylphenyl   372                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-fluoro-5-      444                                             phenoxy       (trifluoromethyl)phenyl                                          3-trifluoromethyl                                                                            3-methoxyphenyl  388                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-bromophenyl    437                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-bromophenyl    437                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-fluoro-3-      444                                             phenoxy       (trifluoromethyl)phenyl                                          3-trifluoromethyl                                                                            3-(trifluoromethoxy)phenyl                                                                      442                                             phenoxy                                                                        3-trifluoromethyl                                                                            9-fluorenon-4-yl 460                                             phenoxy                                                                        3-trifluoromethyl                                                                            isoxazol-5-yl    349                                             phenoxy                                                                        3-trifluoromethyl                                                                            benzofuroxan-5-yl                                                                               416                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-chloropyrid-3-yl                                                                              394                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(4-            465                                             phenoxy       methylphenoxy)pyridin-3-yl                                       3-trifluoromethyl                                                                            pyridin-4-yl     359                                             phenoxy                                                                        3-trifluoromethyl                                                                            anthraquinon-2-yl                                                                               488                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-iodophenyl     484                                             phenoxy                                                                        3-trifluoromethyl                                                                            4-pentylphenyl   428                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-(4-chlorophenylthio)                                                                          502                                             phenoxy       pyridin-3-yl                                                     3-trifluoromethyl                                                                            2,6-dimethylphenyl                                                                              386                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,5-dimethoxyphenyl                                                                             418                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,5-dichloropyridin-3-yl                                                                        428                                             phenoxy                                                                        3-trifluoromethyl                                                                            2-chloro-6-methoxypyridin-                                                                      424                                             phenoxy       4-yl                                                             3-trifluoromethyl                                                                            2,3-dichloropyridin-5-yl                                                                        428                                             phenoxy                                                                        3-trifluoromethyl                                                                            1-naphthyl       422                                             phenoxy                                                                        3-trifluoromethyl                                                                            2,4-dimethoxyphenyl                                                                             418                                             phenoxy                                                                        3-trifluoromethyl                                                                            3,5-             494                                             phenoxy       bis(trifluoromethyl)phenyl                                       3-trifluoromethyl                                                                            2-(4-            486                                             phenoxy       chlorophenoxy)pyridin-3-yl                                       3-trifluoromethyl                                                                            pentafluorophenyl                                                                               448                                             phenoxy                                                                        2,6-dichlorophenoxy                                                                          3,4-dimethoxyphenyl                                                                             419                                             2,6-dichlorophenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       427                                             2,6-dichlorophenoxy                                                                          2,4-difluorophenyl                                                                              395                                             2,6-dichlorophenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       427                                             2,6-dichlorophenoxy                                                                          2-naphthyl       409                                             2,6-dichlorophenoxy                                                                          2-methoxyphenyl  389                                             2,6-dichlorophenoxy                                                                          3,4,5-trimethylphenyl                                                                           449                                             2,6-dichlorophenoxy                                                                          3,4-dichlorophenyl                                                                              428                                             2,6-dichlorophenoxy                                                                          3-bromophenyl    438                                             2,6-dichlorophenoxy                                                                          3-pyridyl        361                                             2,6-dichlorophenoxy                                                                          2-ethoxynaphth-1-yl                                                                             453                                             2,6-dichlorophendxy                                                                          2,3-dichlorophenyl                                                                              428                                             2,6-dichlorophenoxy                                                                          6-chloropyrid-3-yl                                                                              395                                             2,6-dichlorophenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      443                                             2,6-dichlorophenoxy                                                                          2-fluoro-4-      445                                                           (trifluoromethyl)phenyl                                          2,6-dichlorophenoxy                                                                          3-bromothienyl   444                                             2,6-dichlorophenoxy                                                                          2-acetoxyphenyl  417                                             2,6-dichlorophenoxy                                                                          5-methylisoxazol-3-yl                                                                           364                                             2,6-dichlorophenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        468                                             2,6-dichlorophenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      443                                             2,6-dichlorophenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       467                                                           4-yl                                                             2,6-dichlorophenoxy                                                                          2-ethoxyphenyl   403                                             2,6-dichlorophenoxy                                                                          3-chlorothien-2-yl                                                                              400                                             2,6-dichlorophenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       419                                                           methylpyrazol-5-yl                                               2,6-dichlorophenoxy                                                                          3,5-dichlorophenyl                                                                              428                                             2,6-dichlorophenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      434                                             2,6-dichlorophenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       420                                             2,6-dichlorophenoxy                                                                          3-bromopyridin-5-yl                                                                             439                                             2,6-dichlorophenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      381                                                           5-yl                                                             2,6-dichlorophenoxy                                                                          1-methyl-3-(2-(2-                                                                               419                                                           methyl)propyl)pyrazol-5-yl                                       2,6-dichlorophenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       450                                                           2-yl                                                             2,6-dichlorophenoxy                                                                          4-chlorophenyl   394                                             2,6-dichlorophenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        440                                                           triazol-5-yl                                                     2,6-dichlorophenoxy                                                                          benzo[b]thiophen-2-yl                                                                           415                                             2,6-dichlorophenoxy                                                                          3,4-dimethylphenyl                                                                              387                                             2,6-dichlorophenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         452                                             2,6-dichlorophenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      406                                             2,6-dichlorophenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      440                                                           4-yl                                                             2,6-dichlorophenoxy                                                                          4-chloro-1,3-dimethyl                                                                           463                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2,6-dichlorophenoxy                                                                          2-chloro-6-methylpyridin-                                                                       409                                                           4-yl                                                             2,6-dichlorophenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       378                                             2,6-dichlorophenoxy                                                                          1-naphthyl       409                                             2,6-dichlorophenoxy                                                                          2-fluorophenyl   377                                             2,6-dichlorophenoxy                                                                          4-propylphenyl   401                                             2,6-dichlorophenoxy                                                                          3-fluorophenyl   377                                             2,6-dichlorophenoxy                                                                          2,6-difluorophenyl                                                                              395                                             2,6-dichlorophenoxy                                                                          2-chlorophenyl   394                                             2,6-dichlorophenoxy                                                                          3-(chloromethyl)phenyl                                                                          408                                             2,6-dichlorophenoxy                                                                          4-(2-(2-methyl)propyl)                                                                          415                                                           phenyl                                                           2,6-dichlorophenoxy                                                                          3-chlorophenyl   694                                             2,6-dichlorophenoxy                                                                          3,5-dimethoxyphenyl                                                                             419                                             2,6-dichlorophenoxy                                                                          2,6-dichlorophenyl                                                                              428                                             2,6-dichlorophenoxy                                                                          2,4-dichlorophenyl                                                                              428                                             2,6-dichlorophenoxy                                                                          4-fluorophenyl   377                                             2,6-dichlorophenoxy                                                                          4-butylphenyl    415                                             2,6-dichlorophenoxy                                                                          2-methylphenyl   373                                             2,6-dichlorophenoxy                                                                          phenyl           359                                             2,6-dichlorophenoxy                                                                          4-ethylphenyl    387                                             2,6-dichlorophenoxy                                                                          2,3-difluorophenyl                                                                              395                                             2,6-dichlorophenoxy                                                                          2,6-dimethoxyphenyl                                                                             419                                             2,6-dichlorophenoxy                                                                          3,4-difluorophenyl                                                                              395                                             2,6-dichlorophenoxy                                                                          2,5-difluorophenyl                                                                              395                                             2,6-dichlorophenoxy                                                                          4-ethoxyphenyl   403                                             2,6-dichlorophenoxy                                                                          2,4,6-trichlorophenyl                                                                           463                                             2,6-dichlorophenoxy                                                                          3-methylphenyl   373                                             2,6-dichlorophenoxy                                                                          2-fluoro-5-      445                                                           (trifluoromethyl)phenyl                                          2,6-dichlorophenoxy                                                                          3-methoxyphenyl  389                                             2,6-dichlorophenoxy                                                                          2-bromophenyl    438                                             2,6-dichlorophenoxy                                                                          4-bromophenyl    438                                             2,6-dichlorophenoxy                                                                          4-fluoro-3-      445                                                           (trifluoromethyl)phenyl                                          2,6-dichlorophenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      443                                             2,6-dichlorophenoxy                                                                          9-fluorenon-4-yl 461                                             2,6-dichlorophenoxy                                                                          isoxazol-5-yl    350                                             2,6-dichlorophenoxy                                                                          benzofuroxan-5-yl                                                                               417                                             2,6-dichlorophenoxy                                                                          2-chloropyrid-3-yl                                                                              395                                             2,6-dichlorophenoxy                                                                          2-(4-            466                                                           methylphenoxy)pyridin-3-yl                                       2,6-dichlorophenoxy                                                                          pyridin-4-yl     360                                             2,6-dichlorophenoxy                                                                          anthraquinon-2-yl                                                                               489                                             2,6-dichlorophenoxy                                                                          2-iodophenyl     485                                             2,6-dichlorophenoxy                                                                          4-pentylphenyl   429                                             2,6-dichlorophenoxy                                                                          2-(4-chlorophenylthio)                                                                          503                                                           pyridin-3-yl                                                     2,6-dichlorophenoxy                                                                          2,6-dimethylphenyl                                                                              387                                             2,6-dichlorophenoxy                                                                          2,5-dimethoxyphenyl                                                                             419                                             2,6-dichlorophenoxy                                                                          2,5-dichloropyridin-3-yl                                                                        429                                             2,6-dichlorophenoxy                                                                          2-chloro-6-methoxypyridin-                                                                      425                                                           4-yl                                                             2,6-dichlorophenoxy                                                                          2,3-dichloropyridin-5-yl                                                                        429                                             2,6-dichlorophenoxy                                                                          1-naphthyl       413                                             2,6-dichlorophenoxy                                                                          2,4-dimethoxyphenyl                                                                             419                                             2,6-dichlorophenoxy                                                                          3,5-             495                                                           bis(trifluoromethyl)phenyl                                       2,6-dichlorophenoxy                                                                          2-(4-            487                                                           chlorophenoxy)pyridin-3-yl                                       2,6-dichlorophenoxy                                                                          pentafluorophenyl                                                                               449                                             2,4-dichlorophenoxy                                                                          3,4-dimethoxyphenyl                                                                             419                                             2,4-dichlorophenoxy                                                                          2-(trifluoromethyl)phenyl                                                                       427                                             2,4-dichlorophenoxy                                                                          2,4-difluorophenyl                                                                              395                                             2,4-dichlorophenoxy                                                                          3-(trifluoromethyl)phenyl                                                                       427                                             2,4-dichlorophenoxy                                                                          2-naphthyl       409                                             2,4-dichlorophenoxy                                                                          2-methoxyphenyl  389                                             2,4-dichlorophenoxy                                                                          3,4,5-trimethylphenyl                                                                           449                                             2,4-dichlorophenoxy                                                                          3,4-dichlorophenyl                                                                              428                                             2,4-dichlorophenoxy                                                                          3-bromophenyl    438                                             2,4-dichlorophenoxy                                                                          3-pyridyl        361                                             2,4-dichlorophenoxy                                                                          2-ethoxynaphth-1-yl                                                                             453                                             2,4-dichlorophenoxy                                                                          2,3-dichlorophenyl                                                                              428                                             2,4-dichlorophenoxy                                                                          6-chloropyrid-3-yl                                                                              395                                             2,4-dichlorophenoxy                                                                          4-(trifluoromethoxy)phenyl                                                                      443                                             2,4-dichlorophenoxy                                                                          2-fluoro-4-      445                                                           (trifluoromethyl)phenyl                                          2,4-dichlorophenoxy                                                                          3-bromothienyl   444                                             2,4-dichlorophenoxy                                                                          2-acetoxyphenyl  417                                             2,4-dichlorophenoxy                                                                          5-methylisoxazol-3-yl                                                                           364                                             2,4-dichlorophenoxy                                                                          2-(phenylthio)pyrid-3-yl                                                                        468                                             2,4-dichlorophenoxy                                                                          2-(trifluoromethoxy)phenyl                                                                      443                                             2,4-dichlorophenoxy                                                                          1-phenyl-5-propylpyrazin-                                                                       467                                                           4-yl                                                             2,4-dichlorophenoxy                                                                          2-ethoxyphenyl   403                                             2,4-dichlorophenoxy                                                                          3-chlorothien-2-yl                                                                              400                                             2,4-dichlorophenoxy                                                                          1-(2-(2-methyl)propyl)-3-                                                                       419                                                           methylpyrazol-5-yl                                               2,4-dichlorophenoxy                                                                          3,5-dichlorophenyl                                                                              428                                             2,4-dichlorophenoxy                                                                          2-(propylthio)pyridin-3-yl                                                                      434                                             2,4-dichlorophenoxy                                                                          2-(ethylthio)pyridin-3-yl                                                                       420                                             2,4-dichlorophenoxy                                                                          3-bromopyridin-5-yl                                                                             439                                             2,4-dichlorophenoxy                                                                          4-methyl-1,2,3-thiadiazol-                                                                      381                                                           5-yl                                                             2,4-dichlorophenoxy                                                                          1-methyl-3-(2-(2-                                                                               419                                                           methyl)propyl)pyrazol-5-yl                                       2,4-dichlorophenoxy                                                                          3-chlorobenzo[b]thiophen-                                                                       450                                                           2-yl                                                             2,4-dichlorophenoxy                                                                          4-chlorophenyl   394                                             2,4-dichlorophenoxy                                                                          4-methyl-2-phenyl-1,2,3-                                                                        440                                                           triazol-5-yl                                                     2,4-dichlorophenoxy                                                                          benzo[b]thiophen-2-yl                                                                           415                                             2,4-dichlorophenoxy                                                                          3,4-dimethylphenyl                                                                              387                                             2,4-dichlorophenoxy                                                                          2-(phenoxy)pyridin-3-yl                                                                         452                                             2,4-dichlorophenoxy                                                                          2-(methylthio)pyridin-3-yl                                                                      406                                             2,4-dichlorophenoxy                                                                          5-methyl-3-phenylisoxazol-                                                                      440                                                           4-yl                                                             2,4-dichlorophenoxy                                                                          4-chloro-1,3-dimethyl                                                                           463                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               2,4-dichlorophenoxy                                                                          2-chloro-6-methylpyridin-                                                                       409                                                           4-yl                                                             2,4-dichlorophenoxy                                                                          3,5-dimethylisoxazol-4-yl                                                                       378                                             2,4-dichlorophenoxy                                                                          1-naphthyl       409                                             2,4-dichlorophenoxy                                                                          2-fluorophenyl   377                                             2,4-dichlorophenoxy                                                                          4-propylphenyl   401                                             2,4-dichlorophenoxy                                                                          3-fluorophenyl   377                                             2,4-dichlorophenoxy                                                                          2,6-difluorophenyl                                                                              395                                             2,4-dichlorophenoxy                                                                          2-chlorophenyl   394                                             2,4-dichlorophenoxy                                                                          3-(chloromethyl)phenyl                                                                          408                                             2,4-dichlorophenoxy                                                                          4-(2-(2-         415                                                           methyl)propyl)phenyl                                             2,4-dichlorophenoxy                                                                          3-chlorophenyl   694                                             2,4-dichlorophenoxy                                                                          3,5-dimethoxyphenyl                                                                             419                                             2,4-dichlorophenoxy                                                                          2,6-dichlorophenyl                                                                              428                                             2,4-dichlorophenoxy                                                                          2,4-dichlorophenyl                                                                              428                                             2,4-dichlorophenoxy                                                                          4-fluorophenyl   377                                             2,4-dichlorophenoxy                                                                          4-butylphenyl    415                                             2,4-dichlorophenoxy                                                                          2-methylphenyl   373                                             2,4-dichlorophenoxy                                                                          phenyl           359                                             2,4-dichlorophenoxy                                                                          4-ethylphenyl    387                                             2,4-dichlorophenoxy                                                                          2,3-difluorophenyl                                                                              395                                             2,4-dichlorophenoxy                                                                          2,6-dimethoxyphenyl                                                                             419                                             2,4-dichlorophenoxy                                                                          3,4-difluorophenyl                                                                              395                                             2,4-dichlorophenoxy                                                                          2,5-difluorophenyl                                                                              395                                             2,4-dichlorophenoxy                                                                          4-ethoxyphenyl   403                                             2,4-dichlorophenoxy                                                                          2,4,6-trichlorophenyl                                                                           463                                             2,4-dichlorophenoxy                                                                          3-methylphenyl   373                                             2,4-dichlorophenoxy                                                                          2-fluoro-5-      445                                                           (trifluoromethyl)phenyl                                          2,4-dichlorophenoxy                                                                          3-methoxyphenyl  389                                             2,4-dichlorophenoxy                                                                          2-bromophenyl    438                                             2,4-dichlorophenoxy                                                                          4-bromophenyl    438                                             2,4-dichlorophenoxy                                                                          4-fluoro-3-      445                                                           (trifluoromethyl)phenyl                                          2,4-dichlorophenoxy                                                                          3-(trifluoromethoxy)phenyl                                                                      443                                             2,4-dichlorophenoxy                                                                          9-fluorenon-4-yl 461                                             2,4-dichlorophenoxy                                                                          isoxazol-5-yl    350                                             2,4-dichlorophenoxy                                                                          benzofuroxan-5-yl                                                                               417                                             2,4-dichlorophenoxy                                                                          2-chloropyrid-3-yl                                                                              395                                             2,4-dichlorophenoxy                                                                          2-(4-            466                                                           methylphenoxy)pyridin-3-yl                                       2,4-dichlorophenoxy                                                                          pyridin-4-yl     360                                             2,4-dichlorophenoxy                                                                          anthraquinon-2-yl                                                                               489                                             2,4-dichlorophenoxy                                                                          2-iodophenyl     485                                             2,4-dichlorophenoxy                                                                          4-pentylphenyl   429                                             2,4-dichlorophenoxy                                                                          2-(4-chlorophenylthio)                                                                          503                                                           pyridin-3-yl                                                     2,4-dichlorophenoxy                                                                          2,6-dimethylphenyl                                                                              387                                             2,4-dichlorophenoxy                                                                          2,5-dimethoxyphenyl                                                                             419                                             2,4-dichlorophenoxy                                                                          2,5-dichloropyridin-3-yl                                                                        429                                             2,4-dichlorophenoxy                                                                          2-chloro-6-methoxypyridin-                                                                      425                                                           4-yl                                                             2,4-dichlorophenoxy                                                                          2,3-dichloropyridin-5-yl                                                                        429                                             2,4-dichlorophenoxy                                                                          1-naphthyl       413                                             2,4-dichlorophenoxy                                                                          2,4-dimethoxyphenyl                                                                             419                                             2,4-dichlorophenoxy                                                                          3,5-             495                                                           bis(trifluoromethyl)phenyl                                       2,4-dichlorophenoxy                                                                          2-(4-            487                                                           chlorophenoxy)pyridin-3-yl                                       2,4-dichlorophenoxy                                                                          pentafluorophenyl                                                                               449                                             4-chloro-3-   3,4-dimethoxyphenyl                                                                             319                                             methylphenoxy                                                                  4-chloro-3-   2-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-3-   2,4-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-3-   3-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-3-   2-naphthyl       389                                             methylphenoxy                                                                  4-chloro-3-   2-methoxyphenyl  369                                             methylphenoxy                                                                  4-chloro-3-   3,4,5-trimethylphenyl                                                                           429                                             methylphenoxy                                                                  4-chloro-3-   3,4-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-3-   3-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-3-   3-pyridyl        340                                             methylphenoxy                                                                  4-chloro-3-   2-ethoxynaphth-1-yl                                                                             433                                             methylphenoxy                                                                  4-chloro-3-   2,3-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-3-   6-chloropyrid-3-yl                                                                              374                                             methylphenoxy                                                                  4-chloro-3-   4-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-3-   2-fluoro-4-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-3-   3-bromothienyl   424                                             methylphenoxy                                                                  4-chloro-3-   2-acetoxyphenyl  397                                             methylphenoxy                                                                  4-chloro-3-   5-methylisoxazol-3-yl                                                                           344                                             methylphenoxy                                                                  4-chloro-3-   2-(phenylthio)pyrid-3-yl                                                                        448                                             methylphenoxy                                                                  4-chloro-3-   2-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-3-   1-phenyl-5-propylpyrazin-                                                                       447                                             methylphenoxy 4-yl                                                             4-chloro-3-   2-ethoxyphenyl   383                                             methylphenoxy                                                                  4-chloro-3-   3-chlorothien-2-yl                                                                              379                                             methylphenoxy                                                                  4-chloro-3-   1-(2-(2-methyl)propyl)-3-                                                                       399                                             methylphenoxy methylpyrazol-5-yl                                               4-chloro-3-   3,5-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-3-   2-(propylthio)pyridin-3-yl                                                                      414                                             methylphenoxy                                                                  4-chloro-3-   2-(ethylthio)pyridin-3-yl                                                                       400                                             methylphenoxy                                                                  4-chloro-3-   3-bromopyridin-5-yl                                                                             419                                             methylphenoxy                                                                  4-chloro-3-   4-methyl-1,2,3-thiadiazol-                                                                      361                                             methylphenoxy 5-yl                                                             4-chloro-3-   1-methyl-3-(2-(2-                                                                               399                                             methylphenoxy methyl)propyl)pyrazol-5-yl                                       4-chloro-3-   3-chlorobenzo[b]thiophen-                                                                       429                                             methylphenoxy 2-yl                                                             4-chloro-3-   4-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-3-   4-methyl-2-phenyl-1,2,3-                                                                        420                                             methylphenoxy triazol-5-yl                                                     4-chloro-3-   benzo[b]thiophen-2-yl                                                                           395                                             methylphenoxy                                                                  4-chloro-3-   3,4-dimethylphenyl                                                                              367                                             methylphenoxy                                                                  4-chloro-3-   2-(phenoxy)pyridin-3-yl                                                                         432                                             methylphenoxy                                                                  4-chloro-3-   2-(methylthio)pyridin-3-yl                                                                      386                                             methylphenoxy                                                                  4-chloro-3-   5-methyl-3-phenylisoxazol-                                                                      420                                             methylphenoxy 4-yl                                                             4-chloro-3-   4-chloro-1,3-dimethyl                                                                           442                                             methylphenoxy pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-3-   2-chloro-6-methylpyridin-                                                                       388                                             methylphenoxy 4-yl                                                             4-chloro-3-   3,5-dimethylisoxazol-4-yl                                                                       358                                             methylphenoxy                                                                  4-chloro-3-   1-naphthyl       389                                             methylphenoxy                                                                  4-chloro-3-   2-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-3-   4-propylphenyl   381                                             methylphenoxy                                                                  4-chloro-3-   4-(trifluoromethyl)phenyl                                                                       407                                             methylphenoxy                                                                  4-chloro-3-   3-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-3-   2,6-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-3-   2-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-3-   3-(chloromethyl)phenyl                                                                          387                                             methylphenoxy                                                                  4-chloro-3-   4-(2-(2-         395                                             methylphenoxy methyl)propyl)phenyl                                             4-chloro-3-   3-chlorophenyl   373                                             methylphenoxy                                                                  4-chloro-3-   3,5-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-3-   2,6-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-3-   2,4-dichlorophenyl                                                                              408                                             methylphenoxy                                                                  4-chloro-3-   4-fluorophenyl   357                                             methylphenoxy                                                                  4-chloro-3-   4-butylphenyl    395                                             methylphenoxy                                                                  4-chloro-3-   2-methylphenyl   353                                             methylphenoxy                                                                  4-chloro-3-   phenyl           339                                             methylphenoxy                                                                  4-chloro-3-   4-ethylphenyl    367                                             methylphenoxy                                                                  4-chloro-3-   2,3-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-3-   2,6-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-3-   3,4-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-3-   2,5-difluorophenyl                                                                              375                                             methylphenoxy                                                                  4-chloro-3-   4-ethoxyphenyl   383                                             methylphenoxy                                                                  4-chloro-3-   2,4,6-trichlorophenyl                                                                           442                                             methylphenoxy                                                                  4-chloro-3-   3-methylphenyl   353                                             methylphenoxy                                                                  4-chloro-3-   2-fluoro-5-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-3-   3-methoxyphenyl  369                                             methylphenoxy                                                                  4-chloro-3-   2-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-3-   4-bromophenyl    418                                             methylphenoxy                                                                  4-chloro-3-   4-fluoro-3-      425                                             methylphenoxy (trifluoromethyl)phenyl                                          4-chloro-3-   3-(trifluoromethoxy)phenyl                                                                      423                                             methylphenoxy                                                                  4-chloro-3-   9-fluorenon-4-yl 441                                             methylphenoxy                                                                  4-chloro-3-   isoxazol-5-yl    330                                             methylphenoxy                                                                  4-chloro-3-   benzofuroxan-5-yl                                                                               397                                             methylphenoxy                                                                  4-chloro-3-   2-chloropyrid-3-yl                                                                              374                                             methylphenoxy                                                                  4-chloro-3-   2-(4-            446                                             methylphenoxy methylphenoxy)pyridin-3-yl                                       4-chloro-3-   pyridin-4-yl     340                                             methylphenoxy                                                                  4-chloro-3-   anthraquinon-2-yl                                                                               469                                             methylphenoxy                                                                  4-chloro-3-   2-iodophenyl     465                                             methylphenoxy                                                                  4-chloro-3-   4-pentylphenyl   409                                             methylphenoxy                                                                  4-chloro-3-   2-(4-chlorophenylthio)                                                                          482                                             methylphenoxy pyridin-3-yl                                                     4-chloro-3-   2,6-dimethylphenyl                                                                              367                                             methylphenoxy                                                                  4-chloro-3-   2,5-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-3-   2,5-dichloropyridin-3-yl                                                                        409                                             methylphenoxy                                                                  4-chloro-3-   2-chloro-6-methoxypyridin-                                                                      404                                             methylphenoxy 4-yl                                                             4-chloro-3-   2,3-dichloropyridin-5-yl                                                                        409                                             methylphenoxy                                                                  4-chloro-3-   1-naphthyl       403                                             methylphenoxy                                                                  4-chloro-3-   2,4-dimethoxyphenyl                                                                             399                                             methylphenoxy                                                                  4-chloro-3-   3,5-             475                                             methylphenoxy bis(trifluoromethyl)phenyl                                       4-chloro-3-   2-(4-            466                                             methylphenoxy chlorophenoxy)pyridin-3-yl                                       4-chloro-3-   pentafluorophenyl                                                                               429                                             methylphenoxy                                                                  4-chloro-2-   3,4-dimethoxyphenyl                                                                             467                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(trifluoromethyl)phenyl                                                                       475                                             cyclohexylphenoxy                                                              4-chloro-2-   2,4-difluorophenyl                                                                              443                                             cyclohexylphenoxy                                                              4-chloro-2-   3-(trifluoromethyl)phenyl                                                                       475                                             cyclohexylphenoxy                                                              4-chloro-2-   2-naphthyl       457                                             cyclohexylphenoxy                                                              4-chloro-2-   2-methoxyphenyl  437                                             cyclohexylphenoxy                                                              4-chloro-2-   3,4,5-trimethylphenyl                                                                           497                                             cyclohexylphenoxy                                                              4-chloro-2-   3,4-dichlorophenyl                                                                              176                                             cyclohexylphenoxy                                                              4-chloro-2-   3-bromophenyl    486                                             cyclohexylphenoxy                                                              4-chloro-2-   3-pyridyl        408                                             cyclohexylphenoxy                                                              4-chloro-2-   2-ethoxynaphth-1-yl                                                                             501                                             cyclohexylphenoxy                                                              4-chloro-2-   2,3-dichlorophenyl                                                                              476                                             cyclohexylphenoxy                                                              4-chloro-2-   6-chloropyrid-3-yl                                                                              442                                             cyclohexylphenoxy                                                              4-chloro-2-   4-(trifluoromethoxy)phenyl                                                                      491                                             cyclohexylphenoxy                                                              4-chloro-2-   2-fluoro-4-      493                                             cyclohexylphenoxy                                                                            (trifluoromethyl)phenyl                                          4-chloro-2-   3-bromothienyl   492                                             cyclohexylphenoxy                                                              4-chloro-2-   2-acetoxyphenyl  465                                             cyclohexylphenoxy                                                              4-chloro-2-   5-methylisoxazol-3-yl                                                                           412                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(phenylthio)pyrid-3-yl                                                                        516                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(trifluoromethoxy)phenyl                                                                      491                                             cyclohexylphenoxy                                                              4-chloro-2-   1-phenyl-5-propylpyrazin-                                                                       515                                             cyclohexylphenoxy                                                                            4-yl                                                             4-chloro-2-   2-ethoxyphenyl   451                                             cyclohexylphenoxy                                                              4-chloro-2-   3-chlorothien-2-yl                                                                              447                                             cyclohexylphenoxy                                                              4-chloro-2-   1-(2-(2-methyl)propyl)-3-                                                                       467                                             cyclohexylphenoxy                                                                            methylpyrazol-5-yl                                               4-chloro-2-   3,5-dichlorophenyl                                                                              476                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(propylthio)pyridin-3-yl                                                                      482                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(ethylthio)pyridin-3-yl                                                                       468                                             cyclohexylphenoxy                                                              4-chloro-2-   3-bromopyridin-5-yl                                                                             487                                             cyclohexylphenoxy                                                              4-chloro-2-   4-methyl-1,2,3-thiadiazol-                                                                      429                                             cyclohexylphenoxy                                                                            5-yl                                                             4-chloro-2-   1-methyl-3-(2-(2-                                                                               467                                             cyclohexylphenoxy                                                                            methyl)propyl)pyrazol-5-yl                                       4-chloro-2-   3-chlorobenzo[b]thiophen-                                                                       497                                             cyclohexylphenoxy                                                                            2-yl                                                             4-chloro-2-   4-chlorophenyl   441                                             cyclohexylphenoxy                                                              4-chloro-2-   4-methyl-2-phenyl-1,2,3-                                                                        488                                             cyclohexylphenoxy                                                                            triazol-5-yl                                                     4-chloro-2-   benzo[b]thiophen-2-yl                                                                           463                                             cyclohexylphenoxy                                                              4-chloro-2-   3,4-dimethylphenyl                                                                              435                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(phenoxy)pyridin-3-yl                                                                         500                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(methylthio)pyridin-3-yl                                                                      454                                             cyclohexylphenoxy                                                              4-chloro-2-   5-methyl-3-phenylisoxazol-                                                                      488                                             cyclohexylphenoxy                                                                            4-yl                                                             4-chloro-2-   4-chloro-1,3-dimethyl                                                                           510                                             cyclohexylphenoxy                                                                            pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-2-   2-chloro-6-methylpyridin-                                                                       456                                             cyclohexylphenoxy                                                                            4-yl                                                             4-chloro-2-   3,5-dimethylisoxazol-4-yl                                                                       426                                             cyclohexylphenoxy                                                              4-chloro-2-   1-naphthyl       457                                             cyclohexylphenoxy                                                              4-chloro-2-   2-fluorophenyl   425                                             cyclohexylphenoxy                                                              4-chloro-2-   4-propylphenyl   449                                             cyclohexylphenoxy                                                              4-chloro-2-   3-fluorophenyl   425                                             cyclohexylphenoxy                                                              4-chloro-2-   2,6-difluorophenyl                                                                              443                                             cyclohexylphenoxy                                                              4-chloro-2-   2-chlorophenyl   441                                             cyclohexylphenoxy                                                              4-chloro-2-   3-(chloromethyl)phenyl                                                                          455                                             cyclohexylphenoxy                                                              4-chloro-2-   4-(2-(2-         463                                             cyclohexylphenoxy                                                                            methyl)propyl)phenyl                                             4-chloro-2-   3-chlorophenyl   441                                             cyclohexylphenoxy                                                              4-chloro-2-   3,5-dimethoxyphenyl                                                                             467                                             cyclohexylphenoxy                                                              4-chloro-2-   2,6-dichlorophenyl                                                                              476                                             cyclohexylphenoxy                                                              4-chloro-2-   2,4-dichlorophenyl                                                                              476                                             cyclohexylphenoxy                                                              4-chloro-2-   4-fluorophenyl   425                                             cyclohexylphenoxy                                                              4-chloro-2-   4-butylphenyl    463                                             cyclohexylphenoxy                                                              4-chloro-2-   2-methylphenyl   421                                             cyclohexylphenoxy                                                              4-chloro-2-   phenyl           407                                             cyclohexylphenoxy                                                              4-chloro-2-   4-ethylphenyl    435                                             cyclohexylphenoxy                                                              4-chloro-2-   2,3-difluorophenyl                                                                              443                                             cyclohexylphenoxy                                                              4-chloro-2-   2,6-dimethoxyphenyl                                                                             467                                             cyclohexylphenoxy                                                              4-chloro-2-   3,4-difluorophenyl                                                                              443                                             cyclohexylphenoxy                                                              4-chloro-2-   2,5-difluorophenyl                                                                              443                                             cyclohexylphenoxy                                                              4-chloro-2-   4-ethoxyphenyl   451                                             cyclohexylphenoxy                                                              4-chloro-2-   2,4,6-trichlorophenyl                                                                           510                                             cyclohexylphenoxy                                                              4-chloro-2-   3-methylphenyl   421                                             cyclohexylphenoxy                                                              4-chloro-2-   2-fluoro-5-      493                                             cyclohexylphenoxy                                                                            (trifluoromethyl)phenyl                                          4-chloro-2-   3-methoxyphenyl  437                                             cyclohexylphenoxy                                                              4-chloro-2-   2-bromophenyl    486                                             cyclohexylphenoxy                                                              4-chloro-2-   4-bromophenyl    486                                             cyclohexylphenoxy                                                              4-chloro-2-   4-fluoro-3-      493                                             cyclohexylphenoxy                                                                            (trifluoromethyl)phenyl                                          4-chloro-2-   3-(trifluoromethoxy)phenyl                                                                      491                                             cyclohexylphenoxy                                                              4-chloro-2-   9-fluorenon-4-yl 503                                             cyclohexylphenoxy                                                              4-chloro-2-   isoxazol-5-yl    398                                             cyclohexylphenoxy                                                              4-chloro-2-   benzofuroxan-5-yl                                                                               465                                             cyclohexylphenoxy                                                              4-chloro-2-   2-chloropyrid-3-yl                                                                              442                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(4-            514                                             cyclohexylphenoxy                                                                            methylphenoxy)pyridin-3-yl                                       4-chloro-2-   pyridin-4-yl     408                                             cyclohexylphenoxy                                                              4-chloro-2-   anthraquinon-2-yl                                                                               537                                             cyclohexylphenoxy                                                              4-chloro-2-   2-iodophenyl     533                                             cyclohexylphenoxy                                                              4-chloro-2-   4-pentylphenyl   477                                             cyclohexylphenoxy                                                              4-chloro-2-   2-(4-chlorophenylthio)                                                                          550                                             cyclohexylphenoxy                                                                            pyridin-3-yl                                                     4-chloro-2-   2,6-dimethylphenyl                                                                              435                                             cyclohexylphenoxy                                                              4-chloro-2-   2,5-dimethoxyphenyl                                                                             467                                             cyclohexylphenoxy                                                              4-chloro-2-   2,5-dichloropyridin-3-yl                                                                        477                                             cyclohexylphenoxy                                                              4-chloro-2-   2-chloro-6-methoxypyridin-                                                                      472                                             cyclohexylphenoxy                                                                            4-yl                                                             4-chloro-2-   2,3-dichloropyridin-5-yl                                                                        477                                             cyclohexylphenoxy                                                              4-chloro-2-   1-naphthyl       471                                             cyclohexylphenoxy                                                              4-chloro-2-   2,4-dimethoxyphenyl                                                                             467                                             cyclohexylphenoxy                                                              4-chloro-2-   3,5-             546                                             cyclohexylphenoxy                                                                            bis(trifluoromethyl)phenyl                                       4-chloro-2-   2-(4-            534                                             cyclohexylphenoxy                                                                            chlorophenoxy)pyridin-3-yl                                       4-chloro-2-   pentafluorophenyl                                                                               497                                             cyclohexylphenoxy                                                              4-chloro-3,5- 3,4-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(trifluoromethyl)phenyl                                                                       421                                             dimethylphenoxy                                                                4-chloro-3,5- 2,4-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-3,5- 3-(trifluoromethyl)phenyl                                                                       421                                             dimethylphenoxy                                                                4-chloro-3,5- 2-naphthyl       403                                             dimethylphenoxy                                                                4-chloro-3,5- 2-methoxyphenyl  484                                             dimethylphenoxy                                                                4-chloro-3,5- 3,4,5-trimethylphenyl                                                                           443                                             dimethylphenoxy                                                                4-chloro-3,5- 3,4-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-3,5- 3-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-3,5- 3-pyridyl        354                                             dimethylphenoxy                                                                4-chloro-3,5- 2-ethoxynaphth-1-yl                                                                             447                                             dimethylphenoxy                                                                4-chloro-3,5- 2,3-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-3,5- 6-chloropyrid-3-yl                                                                              388                                             dimethylphenoxy                                                                4-chloro-3,5- 4-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-3,5- 2-fluoro-4-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-3,5- 3-bromothienyl   438                                             dimethylphenoxy                                                                4-chloro-3,5- 2-acetoxyphenyl  411                                             dimethylphenoxy                                                                4-chloro-3,5- 5-methylisoxazol-3-yl                                                                           358                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(phenylthio)pyrid-3-yl                                                                        462                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-3,5- 1-phenyl-5-propylpyrazin-                                                                       461                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-3,5- 2-ethoxyphenyl   397                                             dimethylphenoxy                                                                4-chloro-3,5- 3-chlorothien-2-yl                                                                              393                                             dimethylphenoxy                                                                4-chloro-3,5- 1-(2-(2-methyl)propyl)-3-                                                                       413                                             dimethylphenoxy                                                                              methylpyrazol-5-yl                                               4-chloro-3,5- 3,5-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(propylthio)pyridin-3-yl                                                                      428                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(ethylthio)pyridin-3-yl                                                                       414                                             dimethylphenoxy                                                                4-chloro-3,5- 3-bromopyridin-5-yl                                                                             433                                             dimethylphenoxy                                                                4-chloro-3,5- 4-methyl-1,2,3-thiadiazol-                                                                      375                                             dimethylphenoxy                                                                              5-yl                                                             4-chloro-3,5- 1-methyl-3-(2-(2-                                                                               413                                             dimethylphenoxy                                                                              methyl)propyl)pyrazol-5-yl                                       4-chloro-3,5  3-chlorobenzo[b]thiophen-                                                                       443                                             dimethylphenoxy                                                                              2-yl                                                             4-chloro-3,5- 4-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-3,5- 4-methyl-2-phenyl-1,2,3-                                                                        434                                             dimethylphenoxy                                                                              triazol-5-yl                                                     4-chloro-3,5- benzo[b]thiophen-2-yl                                                                           409                                             dimethylphenoxy                                                                4-chloro-3,5- 3,4-dimethylphenyl                                                                              381                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(phenoxy)pyridin-3-yl                                                                         446                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(methylthio)pyridin-3-yl                                                                      400                                             dimethylphenoxy                                                                4-chloro-3,5- 5-methyl-3-phenylisoxazol-                                                                      434                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-3,5- 4-chloro-1,3-dimethyl                                                                           456                                             dimethylphenoxy                                                                              pyrazolo[3 ,4-b]pyridin-3-                                                     yl                                                               4-chloro-3,5- 2-chloro-6-methylpyridin-                                                                       402                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-3,5- 3,5-dimethylisoxazol-4-yl                                                                       372                                             dimethylphenoxy                                                                4-chloro-3,5- 1-naphthyl       403                                             dimethylphenoxy                                                                4-chloro-3,5- 2-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-3,5- 4-propylphenyl   395                                             dimethylphenoxy                                                                4-chloro-3,5- 3-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-3,5- 2,6-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-3,5- 2-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-3,5- 3-(chloromethyl)phenyl                                                                          401                                             dimethylphenoxy                                                                4-chloro-3,5- 4-(2-(2-         409                                             dimethylphenoxy                                                                              methyl)propyl)phenyl                                             4-chloro-3,5- 3-chlorophenyl   387                                             dimethylphenoxy                                                                4-chloro-3,5- 3,5-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-3,5- 2,6-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-3,5- 2,4-dichlorophenyl                                                                              422                                             dimethylphenoxy                                                                4-chloro-3,5- 4-fluorophenyl   371                                             dimethylphenoxy                                                                4-chloro-3,5- 4-butylphenyl    409                                             dimethylphenoxy                                                                4-chloro-3,5- 2-methylphenyl   367                                             dimethylphenoxy                                                                4-chloro-3,5- phenyl           353                                             dimethylphenoxy                                                                4-chloro-3,5- 4-ethylphenyl    381                                             dimethylphenoxy                                                                4-chloro-3,5- 2,3-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-3,5- 2,6-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-3,5- 3,4-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-3,5- 2,5-difluorophenyl                                                                              389                                             dimethylphenoxy                                                                4-chloro-3,5- 4-ethoxyphenyl   397                                             dimethylphenoxy                                                                4-chloro-3,5- 2,4,6-trichlorophenyl                                                                           456                                             dimethylphenoxy                                                                4-chloro-3,5- 3-methylphenyl   367                                             dimethylphenoxy                                                                4-chloro-3,5- 2-fluoro-5-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-3,5- 3-methoxyphenyl  383                                             dimethylphenoxy                                                                4-chloro-3,5- 2-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-3,5- 4-bromophenyl    432                                             dimethylphenoxy                                                                4-chloro-3,5- 4-fluoro-3-      439                                             dimethylphenoxy                                                                              (trifluoromethyl)phenyl                                          4-chloro-3,5- 3-(trifluoromethoxy)phenyl                                                                      437                                             dimethylphenoxy                                                                4-chloro-3,5- 9-fluorenon-4-yl 455                                             dimethylphenoxy                                                                4-chloro-3,5- isoxazol-5-yl    344                                             dimethylphenoxy                                                                4-chloro-3,5- benzofuroxan-5-yl                                                                               411                                             dimethylphenoxy                                                                4-chloro-3,5- 2-chloropyrid-3-yl                                                                              388                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(4-            460                                             dimethylphenoxy                                                                              methylphenoxy)pyridin-3-yl                                       4-chloro-3,5- pyridin-4-yl     354                                             dimethylphenoxy                                                                4-chloro-3,5- anthraquinon-2-yl                                                                               483                                             dimethylphenoxy                                                                4-chloro-3,5- 2-iodophenyl     479                                             dimethylphenoxy                                                                4-chloro-3,5- 4-pentylphenyl   423                                             dimethylphenoxy                                                                4-chloro-3,5- 2-(4-chlorophenylthio)                                                                          496                                             dimethylphenoxy                                                                              pyridin-3-yl                                                     4-chloro-3,5- 2,6-dimethylphenyl                                                                              381                                             dimethylphenoxy                                                                4-chloro-3,5- 2,5-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-3,5- 2,5-dichloropyridin-3-yl                                                                        423                                             dimethylphenoxy                                                                4-chloro-3,5- 2-chloro-6-methoxypyridin-                                                                      418                                             dimethylphenoxy                                                                              4-yl                                                             4-chloro-3,5- 2,3-dichloropyridin-5-yl                                                                        423                                             dimethylphenoxy                                                                4-chloro-3,5- 1-naphthyl       417                                             dimethylphenoxy                                                                4-chloro-3,5- 2,4-dimethoxyphenyl                                                                             413                                             dimethylphenoxy                                                                4-chloro-3,5- 3,5-             489                                             dimethylphenoxy                                                                              bis(trifluoromethyl)phenyl                                       4-chloro-3,5- 2-(4-            480                                             dimethylphenoxy                                                                              chlorophenoxy)pyridin-3-yl                                       4-chloro-3,5- pentafluorophenyl                                                                               443                                             dimethylphenoxy                                                                pyrid-3-yloxy 3,4-dimethoxyphenyl                                                                             351                                             pyrid-3-yloxy 2-(trifluoromethyl)phenyl                                                                       359                                             pyrid-3-yloxy 2,4-difluorophenyl                                                                              327                                             pyrid-3-yloxy 3-(trifluoromethyl)phenyl                                                                       359                                             pyrid-3-yloxy 2-naphthyl       341                                             pyrid-3-yloxy 2-methoxyphenyl  321                                             pyrid-3-yloxy 3,4,5-trimethylphenyl                                                                           381                                             pyrid-3-yloxy 3,4-dichlorophenyl                                                                              360                                             pyrid-3-yloxy 3-bromophenyl    370                                             pyrid-3-yloxy 3-pyridyl        292                                             pyrid-3-yloxy 2-ethoxynaphth-1-yl                                                                             385                                             pyrid-3-yloxy 2,3-dichlorophenyl                                                                              360                                             pyrid-3-yloxy 6-chloropyrid-3-yl                                                                              327                                             pyrid-3-yloxy 4-(trifluoromethoxy)phenyl                                                                      375                                             pyrid-3-yloxy 2-fluoro-4-      377                                                           (trifluoromethyl)phenyl                                          pyrid-3-yloxy 3-bromothienyl   376                                             pyrid-3-yloxy 2-acetoxyphenyl  349                                             pyrid-3-yloxy 5-methylisoxazol-3-yl                                                                           296                                             pyrid-3-yloxy 2-(phenylthio)pyrid-3-yl                                                                        400                                             pyrid-3-yloxy 2-(trifluoromethoxy)phenyl                                                                      375                                             pyrid-3-yloxy 1-phenyl-5-propylpyrazin-                                                                       399                                                           4-yl                                                             pyrid-3-yloxy 2-ethoxyphenyl   335                                             pyrid-3-yloxy 3-chlorothien-2-yl                                                                              332                                             pyrid-3-yloxy 1-(2-(2-methyl)propyl)-3-                                                                       351                                                           methylpyrazol-5-yl                                               pyrid-3-yloxy 3,5-dichlorophenyl                                                                              360                                             pyrid-3-yloxy 2-(propylthio)pyridin-3-yl                                                                      366                                             pyrid-3-yloxy 2-(ethylthio)pyridin-3-yl                                                                       352                                             pyrid-3-yloxy 3-bromopyridin-5-yl                                                                             371                                             pyrid-3-yloxy 4-methyl-1,2,3-thiadiazol-                                                                      313                                                           5-yl                                                             pyrid-3-yloxy 1-methyl-3-(2-(2-                                                                               351                                                           methyl)propyl)pyrazol-5-yl                                       pyrid-3-yloxy 3-chlorobenzo[b]thiophen-                                                                       382                                                           2-yl                                                             pyrid-3-yloxy 4-chlorophenyl   326                                             pyrid-3-yloxy 4-methyl-2-phenyl-1,2,3-                                                                        372                                                           triazol-5-yl                                                     pyrid-3-yloxy benzo[b]thiophen-2-yl                                                                           347                                             pyrid-3-yloxy 3,4-dimethylphenyl                                                                              319                                             pyrid-3-yloxy 2-(phenoxy)pyridin-3-yl                                                                         384                                             pyrid-3-yloxy 2-(methylthio)pyridin-3-yl                                                                      338                                             pyrid-3-yloxy 5-methyl-3-phenylisoxazol-                                                                      372                                                           4-yl                                                             pyrid-3-yloxy 4-chloro-1,3-dimethyl                                                                           395                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               pyrid-3-yloxy 2-chloro-6-methylpyridin-                                                                       341                                                           4-yl                                                             pyrid-3-yloxy 3,5-dimethylisoxazol-4-yl                                                                       310                                             pyrid-3-yloxy 1-naphthyl       341                                             pyrid-3-yloxy 2-fluorophenyl   309                                             pyrid-3-yloxy 4-propylphenyl   333                                             pyrid-3-yloxy 3-fluorophenyl   309                                             pyrid-3-yloxy 2,6-difluorophenyl                                                                              327                                             pyrid-3-yloxy 2-chlorophenyl   326                                             pyrid-3-yloxy 3-(chloromethyl)phenyl                                                                          340                                             pyrid-3-yloxy 4-(2-(2-         347                                                           methyl)propyl)phenyl                                             pyrid-3-yloxy 3-chlorophenyl   326                                             pyrid-3-yloxy 3,5-dimethoxyphenyl                                                                             351                                             pyrid-3-yloxy 2,6-dichlorophenyl                                                                              360                                             pyrid-3-yloxy 2,4-dichlorophenyl                                                                              360                                             pyrid-3-yloxy 4-fluorophenyl   309                                             pyrid-3-yloxy 4-butylphenyl    347                                             pyrid-3-yloxy 2-methylphenyl   305                                             pyrid-3-yloxy phenyl           291                                             pyrid-3-yloxy 4-ethylphenyl    319                                             pyrid-3-yloxy 2,3-difluorophenyl                                                                              327                                             pyrid-3-yloxy 2,6-dimethoxyphenyl                                                                             351                                             pyrid-3-yloxy 3,4-difluorophenyl                                                                              327                                             pyrid-3-yloxy 2,5-difluorophenyl                                                                              327                                             pyrid-3-yloxy 4-ethoxyphenyl   335                                             pyrid-3-yloxy 2,4,6-trichlorophenyl                                                                           395                                             pyrid-3-yloxy 3-methylphenyl   305                                             pyrid-3-yloxy 2-fluoro-5-      377                                                           (trifluoromethyl)phenyl                                          pyrid-3-yloxy 3-methoxyphenyl  321                                             pyrid-3-yloxy 2-bromophenyl    370                                             pyrid-3-yloxy 4-bromophenyl    370                                             pyrid-3-yloxy 4-fluoro-3-      377                                                           (trifluoromethyl)phenyl                                          pyrid-3-yloxy 3-(trifluoromethoxy)phenyl                                                                      375                                             pyrid-3-yloxy 9-fluorenon-4-yl 393                                             pyrid-3-yloxy isoxazol-5-yl    282                                             pyrid-3-yloxy benzofuroxan-5-yl                                                                               349                                             pyrid-3-yloxy 2-chloropyrid-3-yl                                                                              327                                             pyrid-3-yloxy 2-(4-            398                                                           methylphenoxy)pyridin-3-yl                                       pyrid-3-yloxy pyridin-4-yl     292                                             pyrid-3-yloxy anthraquinon-2-yl                                                                               421                                             pyrid-3-yloxy 2-iodophenyl     417                                             pyrid-3-yloxy 4-pentylphenyl   361                                             pyrid-3-yloxy 2-(4-chlorophenylthio)                                                                          435                                                           pyridin-3-yl                                                     pyrid-3-yloxy 2,6-dimethylphenyl                                                                              319                                             pyrid-3-yloxy 2,5-dimethoxyphenyl                                                                             354                                             pyrid-3-yloxy 2,5-dichloropyridin-3-yl                                                                        361                                             pyrid-3-yloxy 2-chloro-6-methoxypyridin-                                                                      357                                                           4-yl                                                             pyrid-3-yloxy 2,3-dichloropyridin-5-yl                                                                        361                                             pyrid-3-yloxy 1-naphthyl       355                                             pyrid-3-yloxy 2,4-dimethoxyphenyl                                                                             351                                             pyrid-3-yloxy 3,5-             427                                                           bis(trifluoromethyl)phenyl                                       pyrid-3-yloxy 2-(4-            419                                                           chlorophenoxy)pyridin-3-yl                                       pyrid-3-yloxy pentafluorophenyl                                                                               381                                             4-bromophenoxy                                                                               3,4-dimethoxyphenyl                                                                             429                                             4-bromophenoxy                                                                               2-(trifluoromethyl)phenyl                                                                       437                                             4-bromophenoxy                                                                               2,4-difluorophenyl                                                                              405                                             4-bromophenoxy                                                                               3-(trifluoromethyl)phenyl                                                                       437                                             4-bromophenoxy                                                                               2-naphthyl       419                                             4-bromophenoxy                                                                               2-methoxyphenyl  399                                             4-bromophenoxy                                                                               3,4,5-trimethylphenyl                                                                           459                                             4-bromophenoxy                                                                               3,4-dichlorophenyl                                                                              438                                             4-bromophenoxy                                                                               3-bromophenyl    448                                             4-bromophenoxy                                                                               3-pyridyl        370                                             4-bromophenoxy                                                                               2-ethoxynaphth-1-yl                                                                             463                                             4-bromophenoxy                                                                               2,3-dichlorophenyl                                                                              438                                             4-bromophenoxy                                                                               6-chloropyrid-3-yl                                                                              405                                             4-bromophenoxy                                                                               4-(trifluoromethoxy)phenyl                                                                      453                                             4-bromophenoxy                                                                               2-fluoro-4-      455                                                           (trifluoromethyl)phenyl                                          4-bromophenoxy                                                                               3-bromothienyl   454                                             4-bromophenoxy                                                                               2-acetoxyphenyl  427                                             4-bromophenoxy                                                                               5-methylisoxazol-3-yl                                                                           374                                             4-bromophenoxy                                                                               2-(phenylthio)pyrid-3-yl                                                                        478                                             4-bromophenoxy                                                                               2-(trifluoromethoxy)phenyl                                                                      453                                             4-bromophenoxy                                                                               1-phenyl-5-propylpyrazin-                                                                       477                                                           4-yl                                                             4-bromophenoxy                                                                               2-ethoxyphenyl   413                                             4-bromophenoxy                                                                               3-chlorothien-2-yl                                                                              410                                             4-bromophenoxy                                                                               1-(2-(2-methyl)propyl)-3-                                                                       429                                                           methylpyrazol-5-yl                                               4-bromophenoxy                                                                               3,5-dichlorophenyl                                                                              438                                             4-bromophenoxy                                                                               2-(propylthio)pyridin-3-yl                                                                      444                                             4-bromophenoxy                                                                               2-(ethylthio)pyridin-3-yl                                                                       430                                             4-bromophenoxy                                                                               3-bromopyridin-5-yl                                                                             449                                             4-bromophenoxy                                                                               4-methyl-1,2,3-thiadiazol-                                                                      391                                                           5-yl                                                             4-bromophenoxy                                                                               1-methyl-3-(2-(2-                                                                               429                                                           methyl)propyl)pyrazol-5-yl                                       4-bromophenoxy                                                                               3-chlorobenzo[b]thiophen-                                                                       460                                                           2-yl                                                             4-bromophenoxy                                                                               4-chlorophenyl   404                                             4-bromophenoxy                                                                               4-methyl-2-phenyl-1,2,3-                                                                        450                                                           triazol-5-yl                                                     4-bromophenoxy                                                                               benzo[b]thiophen-2-yl                                                                           425                                             4-bromophenoxy                                                                               3,4-dimethylphenyl                                                                              397                                             4-bromophenoxy                                                                               2-(phenoxy)pyridin-3-yl                                                                         462                                             4-bromophenoxy                                                                               2-(methylthio)pyridin-3-yl                                                                      416                                             4-bromophenoxy                                                                               5-methyl-3-phenylisoxazol-                                                                      450                                                           4-yl                                                             4-bromophenoxy                                                                               4-chloro-1,3-dimethyl                                                                           473                                                           pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-bromophenoxy                                                                               2-chloro-6-methylpyridin-                                                                       419                                                           4-yl                                                             4-bromophenoxy                                                                               3,5-dimethylisoxazol-4-yl                                                                       388                                             4-bromophenoxy                                                                               1-naphthyl       419                                             4-bromophenoxy                                                                               2-fluorophenyl   387                                             4-bromophenoxy                                                                               4-propylphenyl   411                                             4-bromophenoxy                                                                               3-fluorophenyl   387                                             4-bromophenoxy                                                                               2,6-difluorophenyl                                                                              405                                             4-bromophenoxy                                                                               2-chlorophenyl   414                                             4-bromophenoxy                                                                               3-(chloromethyl)phenyl                                                                          418                                             4-bromophenoxy                                                                               4-(2-(2-         425                                                           methyl)propyl)phenyl                                             4-bromophenoxy                                                                               3-chlorophenyl   404                                             4-bromophenoxy                                                                               3,5-dimethoxyphenyl                                                                             429                                             4-bromophenoxy                                                                               2,6-dichlorophenyl                                                                              438                                             4-bromophenoxy                                                                               2,4-dichlorophenyl                                                                              438                                             4-bromophenoxy                                                                               4-fluorophenyl   387                                             4-bromophenoxy                                                                               4-butylphenyl    425                                             4-bromophenoxy                                                                               2-methylphenyl   383                                             4-bromophenoxy                                                                               phenyl           369                                             4-bromophenoxy                                                                               4-ethylphenyl    397                                             4-bromophenoxy                                                                               2,3-difluorophenyl                                                                              405                                             4-bromophenoxy                                                                               2,6-dimethoxyphenyl                                                                             429                                             4-bromophenoxy                                                                               3,4-difluorophenyl                                                                              405                                             4-bromophenoxy                                                                               2,5-difluorophenyl                                                                              405                                             4-bromophenoxy                                                                               4-ethoxyphenyl   413                                             4-bromophenoxy                                                                               2,4,6-trichlorophenyl                                                                           473                                             4-bromophenoxy                                                                               3-methylphenyl   383                                             4-bromophenoxy                                                                               2-fluoro-5-      455                                                           (trifluoromethyl)phenyl                                          4-bromophenoxy                                                                               3-methoxyphenyl  399                                             4-bromophenoxy                                                                               2-bromophenyl    448                                             4-bromophenoxy                                                                               4-bromophenyl    448                                             4-bromophenoxy                                                                               4-fluoro-3-      455                                                           (trifluoromethyl)phenyl                                          4-bromophenoxy                                                                               3-(trifluoromethoxy)phenyl                                                                      453                                             4-bromophenoxy                                                                               9-fluorenon-4-yl 471                                             4-bromophenoxy                                                                               isoxazol-5-yl    360                                             4-bromophenoxy                                                                               benzofuroxan-5-yl                                                                               427                                             4-bromophenoxy                                                                               2-chloropyrid-3-yl                                                                              360                                             4-bromophenoxy                                                                               2-(4-            476                                                           methylphenoxy)pyridin-3-yl                                       4-bromophenoxy                                                                               pyridin-4-yl     370                                             4-bromophenoxy                                                                               anthraquinon-2-yl                                                                               499                                             4-bromophenoxy                                                                               2-iodophenyl     495                                             4-bromophenoxy                                                                               4-pentylphenyl   439                                             4-bromophenoxy                                                                               2-(4-            513                                                           chlorophenylthio)pyridin-                                                      3-yl                                                             4-bromophenoxy                                                                               2,6-dimethylphenyl                                                                              397                                             4-bromophenoxy                                                                               2,5-dimethoxyphenyl                                                                             429                                             4-bromophenoxy                                                                               2,5-dichloropyridin-3-yl                                                                        439                                             4-bromophenoxy                                                                               2-chloro-6-methoxypyridin-                                                                      435                                                           4-yl                                                             4-bromophenoxy                                                                               2,3-dichloropyridin-5-yl                                                                        439                                             4-bromophenoxy                                                                               1-naphthyl       433                                             4-bromophenoxy                                                                               2,4-dimethoxyphenyl                                                                             429                                             4-bromophenoxy                                                                               3,5-             505                                                           bis(trifluoromethyl)phenyl                                       4-bromophenoxy                                                                               2-(4-            497                                                           chlorophenoxy)pyridin-3-yl                                       4-bromophenoxy                                                                               pentafluorophenyl                                                                               459                                             4-chloro-2-   4-biphenyl       431                                             methylphenylthio                                                               4-chloro-2-   3,4-dimethoxyphenyl                                                                             415                                             methylphenylthio                                                               4-chloro-2-   2-(trifluoromethyl)phenyl                                                                       423                                             methylphenylthio                                                               4-chloro-2-   2,4-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   4-cyanophenyl    380                                             methylphenylthio                                                               4-chloro-2-   3-(trifluoromethyl)phenyl                                                                       423                                             methylphenylthio                                                               4-chloro-2-   3-cyanophenyl    380                                             methylphenylthio                                                               4-chloro-2-   2-naphthyl       405                                             methylphenylthio                                                               4-chloro-2-   2-methoxyphenyl  385                                             methylphenylthio                                                               4-chloro-2-   3,4,5-trimethylphenyl                                                                           445                                             methylphenylthio                                                               4-chloro-2-   4-nitrophenyl    400                                             methylphenylthio                                                               4-chloro-2-   3,4-dichlorophenyl                                                                              424                                             methylphenylthio                                                               4-chloro-2-   5-nitrofuran-2-yl                                                                               390                                             methylphenylthio                                                               4-chloro-2-   3-bromophenyl    434                                             methylphenylthio                                                               4-chloro-2-   3-pyridyl        356                                             methylphenylthio                                                               4-chloro-2-   2-ethoxynaphth-1-yl                                                                             449                                             methylphenylthio                                                               4-chloro-2-   2,3-dichlorophenyl                                                                              424                                             methylphenylthio                                                               4-chloro-2-   3-nitrophenyl    400                                             methylphenylthio                                                               4-chloro-2-   6-chloropyrid-3-yl                                                                              390                                             methylphenylthio                                                               4-chloro-2-   4-(trifluoromethoxy)phenyl                                                                      439                                             methylphenylthio                                                               4-chloro-2-   2-fluoro-4-      441                                             methylphenylthio                                                                             (trifluoromethyl)phenyl                                          4-chloro-2-   3-bromothienyl   440                                             methylphenylthio                                                               4-chloro-2-   2-acetoxyphenyl  413                                             methylphenylthio                                                               4-chloro-2-   5-methylisoxazol-3-yl                                                                           360                                             methylphenylthio                                                               4-chloro-2-   2-(phenylthio)pyrid-3-yl                                                                        464                                             methylphenylthio                                                               4-chloro-2-   2-(trifluoromethoxy)phenyl                                                                      439                                             methylphenylthio                                                               4-chloro-2-   1-phenyl-5-propylpyrazin-                                                                       463                                             methylphenylthio                                                                             4-yl                                                             4-chloro-2-   2-ethoxyphenyl   399                                             methylphenylthio                                                               4-chloro-2-   3-chlorothien-2-yl                                                                              395                                             methylphenylthio                                                               4-chloro-2-   1-(2-(2-methyl)propyl)-3-                                                                       415                                             methylphenylthio                                                                             methylpyrazol-5-yl                                               4-chloro-2-   3,5-dichlorophenyl                                                                              424                                             methylphenylthio                                                               4-chloro-2-   2-(propylthio)pyridin-3-yl                                                                      430                                             methylphenylthio                                                               4-chloro-2-   2-(ethylthio)pyridin-3-yl                                                                       416                                             methylphenylthio                                                               4-chloro-2-   3-bromopyridin-5-yl                                                                             435                                             methylphenylthio                                                               4-chloro-2-   4-methyl-1,2,3-thiadiazol-                                                                      377                                             methylphenylthio                                                                             5-yl                                                             4-chloro-2-   1-methyl-3-(2-(2-                                                                               415                                             methylphenylthio                                                                             methyl)propyl)pyrazol-5-yl                                       4-chloro-2-   3-chlorobenzo[b]thiophen-                                                                       445                                             methylphenylthio                                                                             2-yl                                                             4-chloro-2-   4-chlorophenyl   389                                             methylphenylthio                                                               4-chloro-2-   4-methyl-2-phenyl-1,2,3-                                                                        436                                             methylphenylthio                                                                             triazol-5-yl                                                     4-chloro-2-   benzo[b]thiophen-2-yl                                                                           411                                             methylphenylthio                                                               4-chloro-2-   3,4-dimethylphenyl                                                                              383                                             methylphenylthio                                                               4-chloro-2-   2-(phenoxy)pyridin-3-yl                                                                         448                                             methylphenylthio                                                               4-chloro-2-   2-(methylthio)pyridin-3-yl                                                                      402                                             methylphenylthio                                                               4-chloro-2-   5-methyl-3-phenylisoxazol-                                                                      436                                             methylphenylthio                                                                             4-yl                                                             4-chloro-2-   4-chloro-1,3-dimethyl                                                                           458                                             methylphenylthio                                                                             pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-2-   2-chloro-6-methylpyridin-                                                                       404                                             methylphenylthio                                                                             4-yl                                                             4-chloro-2-   3,5-dimethylisoxazol-4-yl                                                                       374                                             methylphenylthio                                                               4-chloro-2-   1-naphthyl       405                                             methylphenylthio                                                               4-chloro-2-   2-fluorophenyl   373                                             methylphenylthio                                                               4-chloro-2-   4-propylphenyl   397                                             methylphenylthio                                                               4-chloro-2-   4-(trifluoromethyl)phenyl                                                                       423                                             methylphenylthio                                                               4-chloro-2-   3-fluorophenyl   373                                             methylphenylthio                                                               4-chloro-2-   2,6-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   2-chlorophenyl   389                                             methylphenylthio                                                               4-chloro-2-   3-(chloromethyl)phenyl                                                                          403                                             methylphenylthio                                                               4-chloro-2-   4-(2-(2-         411                                             methylphenylthio                                                                             methyl)propyl)phenyl                                             4-chloro-2-   3-chlorophenyl   389                                             methylphenylthio                                                               4-chloro-2-   2-nitrophenyl    400                                             methylphenylthio                                                               4-chloro-2-   3,5-dimethoxyphenyl                                                                             415                                             methylphenylthio                                                               4-chloro-2-   2,6-dichlorophenyl                                                                              424                                             methylphenylthio                                                               4-chloro-2-   2,4-dichlorophenyl                                                                              424                                             methylphenylthio                                                               4-chloro-2-   4-fluorophenyl   373                                             methylphenylthio                                                               4-chloro-2-   4-butylphenyl    411                                             methylphenylthio                                                               4-chloro-2-   2-methylphenyl   369                                             methylphenylthio                                                               4-chloro-2-   phenyl           355                                             methylphenylthio                                                               4-chloro-2-   4-ethylphenyl    383                                             methylphenylthio                                                               4-chloro-2-   2,3-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   2,6-dimethoxyphenyl                                                                             415                                             methylphenylthio                                                               4-chloro-2-   3,4-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   2,5-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   4-ethoxyphenyl   399                                             methylphenylthio                                                               4-chloro-2-   2,4,6-trichlorophenyl                                                                           458                                             methylphenylthio                                                               4-chloro-2-   3-methylphenyl   369                                             methylphenylthio                                                               4-chloro-2-   2-fluoro-5-      441                                             methylphenylthio                                                                             (trifluoromethyl)phenyl                                          4-chloro-2-   3-methoxyphenyl  385                                             methylphenylthio                                                               4-chloro-2-   thien-2-yl       361                                             methylphenylthio                                                               4-chloro-2-   2-bromophenyl    434                                             methylphenylthio                                                               4-chloro-2-   4-bromophenyl    434                                             methylphenylthio                                                               4-chloro-2-   4-fluoro-3-      441                                             methylphenylthio                                                                             (trifluoromethyl)phenyl                                          4-chloro-2-   3-(trifluoromethoxy)phenyl                                                                      439                                             methylphenylthio                                                               4-chloro-2-   9-fluorenon-4-yl 457                                             methylphenylthio                                                               4-chloro-2-   isoxazol-5-yl    346                                             methylphenylthio                                                               4-chloro-2-   benzofuroxan-5-yl                                                                               413                                             methylphenylthio                                                               4-chloro-2-   2-chloropyrid-3-yl                                                                              390                                             methylphenylthio                                                               4-chloro-2-   3,5-difluorophenyl                                                                              391                                             methylphenylthio                                                               4-chloro-2-   2-(4-            462                                             methylphenylthio                                                                             methylphenoxy)pyridin-3-yl                                       4-chloro-2-   pyridin-4-yl     356                                             methylphenylthio                                                               4-chloro-2-   anthraquinon-2-yl                                                                               485                                             methylphenylthio                                                               4-chloro-2-   2-iodophenyl     481                                             methylphenylthio                                                               4-chloro-2-   4-biphenyl       414                                             methylanilino                                                                  4-chloro-2-   3,4-dimethoxyphenyl                                                                             398                                             methylanilino                                                                  4-chloro-2-   2-(trifluoromethyl)phenyl                                                                       406                                             methylanilino                                                                  4-chloro-2-   2,4-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   4-cyanophenyl    363                                             methylanilino                                                                  4-chloro-2-   3-(trifluoromethyl)phenyl                                                                       406                                             methylanilino                                                                  4-chloro-2-   3-cyanophenyl    363                                             methylanilino                                                                  4-chloro-2-   2-naphthyl       388                                             methylanilino                                                                  4-chloro-2-   2-methoxyphenyl  368                                             methylanilino                                                                  4-chloro-2-   3,4,5-trimethylphenyl                                                                           428                                             methylanilino                                                                  4-chloro-2-   4-nitrophenyl    383                                             methylanilino                                                                  4-chloro-2-   3,4-dichlorophenyl                                                                              407                                             methylanilino                                                                  4-chloro-2-   5-nitrofuran-2-yl                                                                               373                                             methylanilino                                                                  4-chloro-2-   3-bromophenyl    417                                             methylanilino                                                                  4-chloro-2-   3-pyridyl        339                                             methylanilino                                                                  4-chloro-2-   2-ethoxynaphth-1-yl                                                                             432                                             methylanilino                                                                  4-chloro-2-   2,3-dichlorophenyl                                                                              407                                             methylanilino                                                                  4-chloro-2-   3-nitrophenyl    383                                             methylanilino                                                                  4-chloro-2-   6-chloropyrid-3-yl                                                                              373                                             methylanilino                                                                  4-chloro-2-   4-(trifluoromethoxy)phenyl                                                                      422                                             methylanilino                                                                  4-chloro-2-   2-fluoro-4-      424                                             methylanilino (trifluoromethyl)phenyl                                          4-chloro-2-   3-bromothienyl   423                                             methylanilino                                                                  4-chloro-2-   2-acetoxyphenyl  396                                             methylanilino                                                                  4-chloro-2-   5-methylisoxazol-3-yl                                                                           343                                             methylanilino                                                                  4-chloro-2-   2-(phenylthio)pyrid-3-yl                                                                        447                                             methylanilino                                                                  4-chloro-2-   2-(trifluoromethoxy)phenyl                                                                      422                                             methylanilino                                                                  4-chloro-2-   1-phenyl-5-propylpyrazin-                                                                       446                                             methylanilino 4-yl                                                             4-chloro-2-   2-ethoxyphenyl   382                                             methylanilino                                                                  4-chloro-2-   3-chlorothien-2-yl                                                                              378                                             methylanilino                                                                  4-chloro-2-   1-(2-(2-methyl)propyl)-3-                                                                       398                                             methylanilino methylpyrazol-5-yl                                               4-chloro-2-   3,5-dichlorophenyl                                                                              407                                             methylanilino                                                                  4-chloro-2-   2-(propylthio)pyridin-3-yl                                                                      413                                             methylanilino                                                                  4-chloro-2-   2-(ethylthio)pyridin-3-yl                                                                       399                                             methylanilino                                                                  4-chloro-2-   3-bromopyridin-5-yl                                                                             418                                             methylanilino                                                                  4-chloro-2-   4-methyl-1,2,3-thiadiazol-                                                                      360                                             methylanilino 5-yl                                                             4-chloro-2-   1-methyl-3-(2-(2-                                                                               398                                             methylanilino methyl)propyl)pyrazol-5-yl                                       4-chloro-2-   3-chlorobenzo[b]thiophen-                                                                       428                                             methylanilino 2-yl                                                             4-chloro-2-   4-chlorophenyl   372                                             methylanilino                                                                  4-chloro-2-   4-methyl-2-phenyl-1,2,3-                                                                        419                                             methylanilino triazol-5-yl                                                     4-chloro-2-   benzo[b]thiophen-2-yl                                                                           394                                             methylanilino                                                                  4-chloro-2-   3,4-dimethylphenyl                                                                              366                                             methylanilino                                                                  4-chloro-2-   2-(phenoxy)pyridin-3-yl                                                                         431                                             methylanilino                                                                  4-chloro-2-   2-(methylthio)pyridin-3-yl                                                                      385                                             methylanilino                                                                  4-chloro-2-   5-methyl-3-phenylisoxazol-                                                                      419                                             methylanilino 4-yl                                                             4-chloro-2-   4-chloro-1,3-dimethyl                                                                           441                                             methylanilino pyrazolo[3,4-b]pyridin-3-                                                      yl                                                               4-chloro-2-   2-chloro-6-methylpyridin-                                                                       387                                             methylanilino 4-yl                                                             4-chloro-2-   3,5-dimethylisoxazol-4-yl                                                                       357                                             methylanilino                                                                  4-chloro-2-   1-naphthyl       388                                             methylanilino                                                                  4-chloro-2-   2-fluorophenyl   356                                             methylanilino                                                                  4-chloro-2-   4-propylphenyl   380                                             methylanilino                                                                  4-chloro-2-   4-(trifluoromethyl)phenyl                                                                       406                                             methylanilino                                                                  4-chloro-2-   3-fluorophenyl   356                                             methylanilino                                                                  4-chloro-2-   2,6-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   2-chlorophenyl   372                                             methylanilino                                                                  4-chloro-2-   3-(chloromethyl)phenyl                                                                          386                                             methylanilino                                                                  4-chloro-2-   4-(2-(2-         394                                             methylanilino methyl)propyl)phenyl                                             4-chloro-2-   3-chlorophenyl   372                                             methylanilino                                                                  4-chloro-2-   2-nitrophenyl    383                                             methylanilino                                                                  4-chloro-2-   3,5-dimethoxyphenyl                                                                             398                                             methylanilino                                                                  4-chloro-2-   2,6-dichlorophenyl                                                                              407                                             methylanilino                                                                  4-chloro-2-   2,4-dichlorophenyl                                                                              407                                             methylanilino                                                                  4-chloro-2-   4-fluorophenyl   356                                             methylanilino                                                                  4-chloro-2-   4-butylphenyl    394                                             methylanilino                                                                  4-chloro-2-   2-methylphenyl   352                                             methylanilino                                                                  4-chloro-2-   phenyl           338                                             methylanilino                                                                  4-chloro-2-   4-ethylphenyl    366                                             methylanilino                                                                  4-chloro-2-   2,3-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   2,6-dimethoxyphenyl                                                                             398                                             methylanilino                                                                  4-chloro-2-   3,4-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   2,5-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   4-ethoxyphenyl   382                                             methylanilino                                                                  4-chloro-2-   2,4,6-trichlorophenyl                                                                           441                                             methylanilino                                                                  4-chloro-2-   3-methylphenyl   352                                             methylanilino                                                                  4-chloro-2-   2-fluoro-5-      424                                             methylanilino (trifluoromethyl)phenyl                                          4-chloro-2-   3-methoxyphenyl  368                                             methylanilino                                                                  4-chloro-2-   thien-2-yl       344                                             methylanilino                                                                  4-chloro-2-   2-bromophenyl    417                                             methylanilino                                                                  4-chloro-2-   4-bromophenyl    417                                             methylanilino                                                                  4-chloro-2-   4-fluoro-3-      424                                             methylanilino (trifluoromethyl)phenyl                                          4-chloro-2-   3-(trifluoromethoxy)phenyl                                                                      422                                             methylanilino                                                                  4-chloro-2-   9-fluorenon-4-yl 440                                             methylanilino                                                                  4-chloro-2-   isoxazol-5-yl    329                                             methylanilino                                                                  4-chloro-2-   benzofuroxan-5-yl                                                                               396                                             methylanilino                                                                  4-chloro-2-   2-chloropyrid-3-yl                                                                              373                                             methylanilino                                                                  4-chloro-2-   3,5-difluorophenyl                                                                              374                                             methylanilino                                                                  4-chloro-2-   2-(4-            445                                             methylanilino methylphenoxy)pyridin-3-yl                                       4-chloro-2-   pyridin-4-yl     339                                             methylanilino                                                                  4-chloro-2-   anthraquinon-2-yl                                                                               468                                             methylanilino                                                                  4-chloro-2-   2-iodophenyl     464                                             methylanilino                                                                  ______________________________________                                    

The compounds listed in Table 7 can be prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride according to the general procedure above.

                  TABLE 7                                                          ______________________________________                                         R.sup.1 X          R.sup.3                                                     ______________________________________                                         4-chloro-2-methylphenoxy                                                                          3,4-difluorphenyl                                           4-chloro-2-methylphenoxy                                                                          4-pentylphenyl                                              4-chloro-2-methylphenoxy                                                                          2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                4-chloro-2-methylphenoxy                                                                          2,6-dimethylphenyl                                          4-chloro-2-methylphenoxy                                                                          2,5-dimethoxyphenyl                                         4-chloro-2-methylphenoxy                                                                          2,5-dichloropyridin-3-yl                                    4-chloro-2-methylphenoxy                                                                          2-chloro-6-methoxypyridin-                                                     4-yl                                                        4-chloro-2-methylphenoxy                                                                          2,3-dichloropyridin-5-yl                                    4-chloro-2-methylphenoxy                                                                          1-naphthyl                                                  4-chloro-2-methylphenoxy                                                                          2,4-dimethoxyphenyl                                         4-chloro-2-methylphenoxy                                                                          3,5-                                                                           bis(trifluoromethyl)phenyl                                  4-chloro-2-methylphenoxy                                                                          2-(4-                                                                          chlorophenoxy)pyridin-3-yl                                  4-chloro-2-methylphenoxy                                                                          pentafluorophenyl                                           1-naphthoxy        4-pentylphenyl                                              1-naphthoxy        2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                1-naphthoxy        2,6-dimethylphenyl                                          1-naphthoxy        2,5-dimethoxyphenyl                                         1-naphthoxy        2,5-dichloropyridin-3-yl                                    1-naphthoxy        2-chloro-6-methoxypyridin-                                                     4-yl                                                        1-naphthoxy        2,3-dichloropyridin-5-yl                                    1-naphthoxy        1-naphthyl                                                  1-naphthoxy        2,4-dimethoxyphenyl                                         1-naphthoxy        3,5-bis(trifluoromethyl)                                                       phenyl                                                      1-naphthoxy        2-(4-                                                                          chlorophenoxy) pyridin-3 -yl                                1-naphthoxy        pentafluorophenyl                                           2-(2-propyl)phenoxy                                                                               4-pentylphenyl                                              2-(2-propyl)phenoxy                                                                               2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                2-(2-propyl)phenoxy                                                                               2,6-dimethylphenyl                                          2-(2-propyl)phenoxy                                                                               2,5-dimethoxyphenyl                                         2-(2-propyl)phenoxy                                                                               2,5-dichloropyridin-3-yl                                    2-(2-propyl)phenoxy                                                                               2-chloro-6-methoxypyridin-                                                     4-yl                                                        2-(2-propyl)phenoxy                                                                               2,3-dichloropyridin-5-yl                                    2-(2-propyl)phenoxy                                                                               1-naphthyl                                                  2-(2-propyl)phenoxy                                                                               2,4-dimethoxyphenyl                                         2-(2-propyl)phenoxy                                                                               3,5-bis (trifluoromethyl)                                                      phenyl                                                      2-(2-propyl)phenoxy                                                                               2-(4-                                                                          chlorophenoxy)pyridin-3-yl                                  2-(2-propyl)phenoxy                                                                               pentafluorophenyl                                           3-fluoro-5-methylphenoxy                                                                          4-pentylphenyl                                              3-fluoro-5-methylphenoxy                                                                          2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                3-fluoro-5-methylphenoxy                                                                          2,6-dimethylphenyl                                          3-fluoro-5-methylphenoxy                                                                          2,5-dimethoxyphenyl                                         3-fluoro-5-methylphenoxy                                                                          2,5-dichloropyridin-3-yl                                    3-fluoro-5-methylphenoxy                                                                          2-chloro-6-methoxypyridin-                                                     4-yl                                                        3-fluoro-5-methylphenoxy                                                                          2,3-dichloropyridin-5-yl                                    3-fluoro-5-methylphenoxy                                                                          1-naphthyl                                                  3-fluoro-5-methylphenoxy                                                                          2,4-dimethoxyphenyl                                         3-fluoro-5-methylphenoxy                                                                          3,5-bis(trifluoromethyl)                                                       phenyl                                                      3-fluoro-5-methylphenoxy                                                                          2-(4-                                                                          chlorophenoxy) pyridin-3-yl                                 3-fluoro-5-methylphenoxy                                                                          pentafluorophenyl                                           2-methylpyrid-3-yloxy                                                                             4-pentylphenyl                                              2-methylpyrid-3-yloxy                                                                             2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                2-methylpyrid-3-yloxy                                                                             2,6-dimethylphenyl                                          2-methylpyrid-3-yloxy                                                                             2,5-dimethoxyphenyl                                         2-methylpyrid-3-yloxy                                                                             2,5-dichloropyridin-3-yl                                    2-methylpyrid-3-yloxy                                                                             2-chloro-6-methoxypyridin-                                                     4-yl                                                        2-methylpyrid-3-yloxy                                                                             2,3-dichloropyridin-5-yl                                    2-methylpyrid-3-yloxy                                                                             1-naphthyl                                                  2-methylpyrid-3-yloxy                                                                             2,4-dimethoxyphenyl                                         2-methylpyrid-3-yloxy                                                                             3,5-bis(trifluoromethyl)                                                       phenyl                                                      2-methylpyrid-3-yloxy                                                                             2-(4-                                                                          chlorophenoxy)pyridin-3-yl                                  2-methylpyrid-3-yloxy                                                                             pentafluorophenyl                                           4-methoxyphenoxy   4-biphenyl                                                  4-methoxyphenoxy   4-cyanophenyl                                               4-methoxyphenoxy   3-cyanophenyl                                               4-methoxyphenoxy   4-nitrophenyl                                               4-methoxyphenoxy   5-nitrofuran-2-yl                                           4-methoxyphenoxy   3-nitrophenyl                                               4-methoxyphenoxy   4-(trifluoromethyl)phenyl                                   4-methoxyphenoxy   2-nitrophenyl                                               4-methoxyphenoxy   thien-2-yl                                                  2-(2-propoxy)phenoxy                                                                              4-biphenyl                                                  2-(2-propoxy)phenoxy                                                                              4-cyanophenyl                                               2-(2-propoxy)phenoxy                                                                              3-cyanophenyl                                               2-(2-propoxy)phenoxy                                                                              4-nitrophenyl                                               2-(2-propoxy)phenoxy                                                                              5-nitrofuran-2-yl                                           2-(2-propoxy)phenoxy                                                                              3-nitrophenyl                                               2-(2-propoxy)phenoxy                                                                              2-nitrophenyl                                               2-(2-propoxy)phenoxy                                                                              thien-2-yl                                                  2-(2-propoxy)phenoxy                                                                              3,5-difluorophenyl                                          4-fluorophenoxy    4-biphenyl                                                  4-fluorophenoxy    4-cyanophenyl                                               4-fluorophenoxy    3-cyanophenyl                                               4-fluorophenoxy    4-nitrophenyl                                               4-fluorophenoxy    5-nitrofuran-2-yl                                           4-fluorophenoxy    3-nitrophenyl                                               4-fluorophenoxy    2-nitrophenyl                                               4-fluorophenoxy    4-(trifluoromethyl)phenyl                                   4-fluorophenoxy    thien-2-yl                                                  4-fluorophenoxy    3,5-difluorophenyl                                          4-chlorophenoxy    4-biphenyl                                                  4-chlorophenoxy    4-cyanophenyl                                               4-chlorophenoxy    3-cyanophenyl                                               4-chlorophenoxy    4-nitrophenyl                                               4-chlorophenoxy    5-nitrofuran-2-yl                                           4-chlorophenoxy    3-nitrophenyl                                               4-chlorophenoxy    2-nitrophenyl                                               4-chlorophenoxy    4-(trifluoromethyl)phenyl                                   4-chlorophenoxy    thien-2-yl                                                  4-chlorophenoxy    3,5-difluorophenyl                                          2,4-difluorophenoxy                                                                               4-biphenyl                                                  2,4-difluorophenoxy                                                                               4-cyanophenyl                                               2,4-difluorophenoxy                                                                               3-cyanophenyl                                               2,4-difluorophenoxy                                                                               4-nitrophenyl                                               2,4-difluorophenoxy                                                                               5-nitrofuran-2-yl                                           2,4-difluorophenoxy                                                                               3-nitrophenyl                                               2,4-difluorophenoxy                                                                               4-(trifluoromethyl)phenyl                                   2,4-difluorophenoxy                                                                               2-nitrophenyl                                               4-chloro-2,5-      4-biphenyl                                                  dimethylphenoxy                                                                4-chloro-2,5-      4-cyanophenyl                                               dimethylphenoxy                                                                4-chloro-2,5-      3-cyanophenyl                                               dimethylphenoxy                                                                4-chloro-2,5-      4-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-2,5-      5-nitrofuran-2-yl                                           dimethylphenoxy                                                                4-chloro-2,5-      3-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-2,5-      4-(trifluoromethyl)phenyl                                   dimethylphenoxy                                                                4-chloro-2,5-      2-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-2,5-      thien-2-yl                                                  dimethylphenoxy                                                                4-chloro-2,5-      3,5-difluorophenyl                                          dimethylphenoxy                                                                4-methoxyphenoxy   3,5-difluorophenyl                                          2-(2-propoxy)phenoxy                                                                              4-(trifluoromethyl)phenyl                                   2,4-difluorophenoxy                                                                               thien-2-yl                                                  2,4-difluorophenoxy                                                                               3,5-difluorophenyl                                          4-thiomethylphenoxy                                                                               4-biphenyl                                                  4-thiomethylphenoxy                                                                               4-cyanophenyl                                               4-thiomethylphenoxy                                                                               3-cyanophenyl                                               4-thiomethylphenoxy                                                                               4-nitrophenyl                                               4-thiomethylphenoxy                                                                               5-nitrofuran-2-yl                                           4-thiomethylphenoxy                                                                               3-nitrophenyl                                               4-thiomethylphenoxy                                                                               4-(trifluoromethyl)phenyl                                   4-thiomethylphenoxy                                                                               2-nitrophenyl                                               4-thiomethylphenoxy                                                                               thien-2-yl                                                  4-thiomethylphenoxy                                                                               3,5-difluorophenyl                                          4-(2-(2-methyl)propyl)                                                                            4-biphenyl                                                  phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            4-cyanophenyl                                               phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            3-cyanophenyl                                               phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            4-nitrophenyl                                               phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            5-nitrofuran-2-yl                                           phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            3-nitrophenyl                                               phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            4-(trifluoromethyl)phenyl                                   phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            2-nitrophenyl                                               phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            thien-2-yl                                                  phenoxy                                                                        4-(2-(2-methyl)propyl)                                                                            3,5-difluorophenyl                                          phenoxy                                                                        2,3-dimethylphenoxy                                                                               4-biphenyl                                                  2,3-dimethylphenoxy                                                                               4-cyanophenyl                                               2,3-dimethylphenoxy                                                                               3-cyanophenyl                                               2,3-dimethylphenoxy                                                                               4-nitrophenyl                                               2,3-dimethylphenoxy                                                                               5-nitrofuran-2-yl                                           2,3-dimethylphenoxy                                                                               3-nitrophenyl                                               2,3-dimethylphenoxy                                                                               4-(trifluoromethyl)phenyl                                   2,3-dimethylphenoxy                                                                               2-nitrophenyl                                               2,3-dimethylphenoxy                                                                               thien-2-yl                                                  2,3-dimethylphenoxy                                                                               3,5-difluorophenyl                                          3,5-(bis-2-propyl)phenoxy                                                                         4-biphenyl                                                  3,5-(bis-2-propyl)phenoxy                                                                         4-cyanophenyl                                               3,5-(bis-2-propyl)phenoxy                                                                         3-cyanophenyl                                               3,5-(bis-2-propyl)phenoxy                                                                         4-nitrophenyl                                               3,5-(bis-2-propyl)phenoxy                                                                         5-nitrofuran-2-yl                                           3,5-(bis-2-propyl)phenoxy                                                                         3-nitrophenyl                                               3,5-(bis-2-propyl)phenoxy                                                                         4-(trifluoromethyl)phenyl                                   3,5-(bis-2-propyl)phenoxy                                                                         2-nitrophenyl                                               3,5-(bis-2-propyl)phenoxy                                                                         thien-2-yl                                                  3,5-(bis-2-propyl)phenoxy                                                                         3,5-difluorophenyl                                          3-trifluoromethyl phenoxy                                                                         4-biphenyl                                                  3-trifluoromethyl phenoxy                                                                         4-cyanophenyl                                               3-trifluoromethyl phenoxy                                                                         3-cyanophenyl                                               3-trifluoromethyl phenoxy                                                                         4-nitrophenyl                                               3-trifluoromethyl phenoxy                                                                         5-nitrofuran-2-yl                                           3-trifluoromethyl phenoxy                                                                         3-nitrophenyl                                               3-trifluoromethyl phenoxy                                                                         4-(trifluoromethyl)phenyl                                   3-trifluoromethyl phenoxy                                                                         2-nitrophenyl                                               3-trifluoromethyl phenoxy                                                                         thien-2-yl                                                  3-trifluoromethyl phenoxy                                                                         3,5-difluorophenyl                                          2,6-dichlorophenoxy                                                                               4-biphenyl                                                  2,6-dichlorophenoxy                                                                               4-cyanophenyl                                               2,6-dichlorophenoxy                                                                               3-cyanophenyl                                               2,6-dichlorophenoxy                                                                               4-nitrophenyl                                               2,6-dichlorophenoxy                                                                               5-nitrofuran-2-yl                                           2,6-dichlorophenoxy                                                                               3-nitrophenyl                                               2,6-dichlorophenoxy                                                                               4-(trifluoromethyl)phenyl                                   2,6-dichlorophenoxy                                                                               2-nitrophenyl                                               2,6-dichlorophenoxy                                                                               thien-2-yl                                                  2,6-dichlorophenoxy                                                                               3,5-difluorophenyl                                          2,4-dichlorophenoxy                                                                               4-biphenyl                                                  2,4-dichlorophenoxy                                                                               4-cyanophenyl                                               2,4-dichlorophenoxy                                                                               3-cyanophenyl                                               2,4-dichlorophenoxy                                                                               4-nitrophenyl                                               2,4-dichlorophenoxy                                                                               5-nitrofuran-2-yl                                           2,4-dichlorophenoxy                                                                               3-nitrophenyl                                               2,4-dichlorophenoxy                                                                               4-(trifluoromethyl)phenyl                                   2,4-dichlorophenoxy                                                                               2-nitrophenyl                                               2,4-dichlorophenoxy                                                                               thien-2-yl                                                  2,4-dichlorophenoxy                                                                               3,5-difluorophenyl                                          4-chloro-3-methylphenoxy                                                                          4-biphenyl                                                  4-chloro-3-methylphenoxy                                                                          4-cyanophenyl                                               4-chloro-3-methylphenoxy                                                                          3-cyanophenyl                                               4-chloro-3-methylphenoxy                                                                          4-nitrophenyl                                               4-chloro-3-methylphenoxy                                                                          5-nitrofuran-2-yl                                           4-chloro-3-methylphenoxy                                                                          3-nitrophenyl                                               4-chloro-3-methylphenoxy                                                                          2-nitrophenyl                                               4-chloro-3-methylphenoxy                                                                          thien-2-yl                                                  4-chloro-3-methylphenoxy                                                                          3,5-difluorophenyl                                          4-chloro-2-        4-biphenyl                                                  cyclohexylphenoxy                                                              4-chloro-2-        4-cyanophenyl                                               cyclohexylphenoxy                                                              4-chloro-2 -       3 -cyanophenyl                                              cyclohexylphenoxy                                                              4-chloro-2-        4-nitrophenyl                                               cyclohexylphenoxy                                                              4-chloro-2-        5-nitrofuran-2-yl                                           cyclohexylphenoxy                                                              4-chloro-2-        3-nitrophenyl                                               cyclohexylphenoxy                                                              4-chloro-2-        4-(trifluoromethyl)phenyl                                   cyclohexylphenoxy                                                              4-chloro-2-        2-nitrophenyl                                               cyclohexylphenoxy                                                              4-chloro-2-        thien-2-yl                                                  cyclohexylphenoxy                                                              4-chloro-2-        3,5-difluorophenyl                                          cyclohexylphenoxy                                                              4-chloro-3,5-      4-biphenyl                                                  dimethylphenoxy                                                                4-chloro-3,5-      4-cyanophenyl                                               dimethylphenoxy                                                                4-chloro-3,5-      3-cyanophenyl                                               dimethylphenoxy                                                                4-chloro-3,5-      4-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-3,5-      5-nitrofuran-2-yl                                           dimethylphenoxy                                                                4-chloro-3,5-      3-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-3,5-      4-(trifluoromethyl)phenyl                                   dimethylphenoxy                                                                4-chloro-3,5-      2-nitrophenyl                                               dimethylphenoxy                                                                4-chloro-3,5-      thien-2-yl                                                  dimethylphenoxy                                                                4-chloro-3,5-      3,5-difluorophenyl                                          dimethylphenoxy                                                                pyrid-3-yloxy      4-biphenyl                                                  pyrid-3-yloxy      4-cyanophenyl                                               pyrid-3-yloxy      3-cyanophenyl                                               pyrid-3-yloxy      4-nitrophenyl                                               pyrid-3-yloxy      5-nitrofuran-2-yl                                           pyrid-3-yloxy      3-nitrophenyl                                               pyrid-3-yloxy      4-(trifluoromethyl)phenyl                                   pyrid-3-yloxy      2-nitrophenyl                                               pyrid-3-yloxy      thien-2-yl                                                  pyrid-3-yloxy      3,5-difluorophenyl                                          4-bromophenoxy     4-biphenyl                                                  4-bromophenoxy     4-cyanophenyl                                               4-bromophenoxy     3-cyanophenyl                                               4-bromophenoxy     4-nitrophenyl                                               4-bromophenoxy     5-nitrofuran-2-yl                                           4-bromophenoxy     3-nitrophenyl                                               4-bromophenoxy     4-(trifluoromethyl)phenyl                                   4-bromophenoxy     2-nitrophenyl                                               4-bromophenoxy     thien-2-yl                                                  4-bromophenoxy     3,5-difluorophenyl                                          4-chloro-2-        4-pentylphenyl                                              methylphenylthio                                                               4-chloro-2-        2-(4-chlorophenylthio)                                      methylphenylthio   pyridin-3-yl                                                4-chloro-2-        2,6-dimethylphenyl                                          methylphenylthio                                                               4-chloro-2-        2,5-dimethoxyphenyl                                         methylphenylthio                                                               4-chloro-2-        2,5-dichloropyridin-3-yl                                    methylphenylthio                                                               4-chloro-2-        2-chloro-6-methoxypyridin-                                  methylphenylthio   4-yl                                                        4-chloro-2-        2,3-dichloropyridin-5-yl                                    methylphenylthio                                                               4-chloro-2-        1-naphthyl                                                  methylphenylthio                                                               4-chloro-2-        2,4-dimethoxyphenyl                                         methylphenylthio                                                               4-chloro-2-        3,5-bis(trifluoromethyl)                                    methylphenylthio   phenyl                                                      4-chloro-2-        2-(4-                                                       methylphenylthio   chlorophenoxy)pyridin-3-yl                                  4-chloro-2-        pentafluorophenyl                                           methylphenylthio                                                               4-chloro-2-methylanilino                                                                          4-pentylphenyl                                              4-chloro-2-methylanilino                                                                          2-(4-chlorophenylthio)                                                         pyridin-3-yl                                                4-chloro-2-methylanilino                                                                          2,6-dimethylphenyl                                          4-chloro-2-methylanilino                                                                          2,5-dimethoxyphenyl                                         4-chloro-2-methylanilino                                                                          2,5-dichloropyridin-3-yl                                    4-chloro-2-methylanilino                                                                          2-chloro-6-methoxypyridin-                                                     4-yl                                                        4-chloro-2-methylanilino                                                                          2,3-dichloropyridin-5-yl                                    4-chloro-2-methylanilino                                                                          1-naphthyl                                                  4-chloro-2-methylanilino                                                                          2,4-dimethoxyphenyl                                         4-chloro-2-methylanilino                                                                          3,5-                                                                           bis(trifluoromethyl)phenyl                                  4-chloro-2-methylanilino                                                                          2-(4-                                                                          chlorophenoxy)pyridin-3-yl                                  4-chloro-2-methylanilino                                                                          pentafluorophenyl                                           ______________________________________                                    

EXAMPLE 19 ##STR22## General procedure for the synthesis of 6-(substituted-amino)-N-substituted nicotinamides

Step A. General procedure for the preparation of 6-chloro-N-substituted nicotinamide

To a suspension of 6-chloronicotinoyl chloride (1.76 g, 10.0 mmol) in dry dichloromethane (10 mL) was added the amine (R³ R⁴ NH) (10.0 mmol) followed by the dropwise addition of triethylamine (1.7 mL, 12.2 mmol). After stirring for 40 min. at room temperature, the mixture was diluted with dichloromethane, washed with aqueous 1 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate and water, dried over sodium sulfate and concentrated to dryness under reduce pressure to afford the desired nicotinamide.

The following compounds were prepared according to this procedure using the appropriate substituted amine:

6-Chloro-N-o-tolylnicotinamide: MS (m/z): 247/249 (M+H)⁺ ; C₁₃ H₁₁ Cl₁ N₂ O₁ requires 246.5.

6-Chloro-N-(2-fluorophenyl)nicotinamide: MS (m/z): 251/253 (M+H)⁺ ; C₁₂ H₈ Cl₁ F₁ N₂ O₁ requires 250.7.

6-Chloro-N-(2,6-dimethylphenyl)nicotinamide: MS (m/z): 261/263 (M+H)⁺ ; C₁₄ H₁₃ Cl₁ N₂ O₁ requires 260.7.

6-Chloro-N-(2-phenoxyphenyl)nicotinamide: MS (m/z): 325/327 (M+H)⁺ ; C₁₈ H₁₃ Cl₁ N₂ O₁ requires 324.8.

6-Chloro-N-phenylnicotinamide: MS (m/z): 233/235 (M+H)⁺ ; C₁₂ H₈ Cl₁ N₂ O₁ requires 232.7.

6-Chloro-N-(2,4-difluorophenyl)nicotinamide: MS (m/z): 269/271 (M+H)⁺ ; C₁₂ H₇ Cl₁ F₂ N₂ O₁ requires 268.6.

6-Chloro-N-(2,6-diisopropylphenyl)nicotinamide: MS (m/z): 317/319 (M+H)⁺ ; C₁₈ H₂₁ Cl₁ N₂ O₁ requires 316.8.

6-Chloro-N-(4-chlorophenyl)-N-methylnicotinamide: MS (m/z): 281/283 (M+H)⁺ ; C₁₃ H₁₀ Cl₂ N₂ O₁ requires 281.1.

6-Chloro-N-(2,4-dimethoxyphenyl)nicotinamide: MS (m/z): 293/295 (M+H)⁺ ; C₁₄ H₁₃ Cl₁ N₂ O₃ requires 292.7.

6-Chloro-N-(3-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)⁺ ; C₁₃ H₁₁ Cl₁ N₂ O₂ requires 262.7.

6-Chloro-N-(4-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)⁺ ; C₁₃ H₁₁ Cl₁ N₂ O₂ requires 262.7.

6-Chloro-N-(2-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)⁺ ; C₁₃ H₁₁ Cl₁ N₂ O₂ requires 262.7.

6-Chloro-N-methyl-N-phenylnicotinamide: MS (m/z): 247/249 (M+H)⁺ ; C₁₃ H₁₁ Cl₂ N₂ O₁ requires 246.7.

N-Benzyl-6-chloronicotinamide: MS (m/z): 247/249 (M+H)⁺ ; C₁₃ H₁₁ Cl₁ N₂ O₁ requires 246.7.

Step B. General procedure for the preparation of 6-(substituted-amino)-N-substituted nicotinamides

A mixture of the 6-chloro-N-substituted nicotinamide (12.5 mmol) and amine (R¹ NH₂ or R¹ NHCH₃) (20 mmol) in ethylene glycol (50 mL) or pyridine (alkylamines) (50 mL) was heated to 140° C. for 20 hours. After cooling to room temperature, the mixture was diluted with dichloromethane/methanol (9:1, 250 mL) and filtered through a plug of silica gel, washing with additional dichloromethane/methanol (9:1, 250 mL). Concentration under reduced pressure afforded the desired 6-(substituted-amino)-N-substituted nicotinamide.

The compounds listed in Tables 8-11 were prepared from 6-chloro-N-substituted nicotinamides compounds and the appropriate amine according to the general procedure above.

                  TABLE 8                                                          ______________________________________                                          ##STR23##                                                                                                    MS                                              R.sup.3        R.sup.1         (m/z)                                           ______________________________________                                         o-tolyl        phenyl          303                                             o-tolyl        o-tolyl         317                                             o-tolyl        4-chloro-2-methylphenyl                                                                        352                                             o-tolyl        2-fluorophenyl  321                                             o-tolyl        3-fluorophenyl  321                                             o-tolyl        4-fluorophenyl  321                                             o-tolyl        2,4-difluorophenyl                                                                             339                                             o-tolyl        2-methoxyphenyl 333                                             o-tolyl        3-methoxyphenyl 333                                             o-tolyl        4-methoxyphenyl 333                                             o-tolyl        2,4-dimethoxyphenyl                                                                            363                                             o-tolyl        2-phenoxyphenyl 395                                             o-tolyl        3-phenoxyphenyl 395                                             o-tolyl        4-phenoxyphenyl 395                                             o-tolyl        4-biphenyl      379                                             o-tolyl        4-benzylphenyl  393                                             o-tolyl        4-(trifluoromethoxy)phenyl                                                                     387                                             o-tolyl        cyclohexyl      309                                             o-tolyl        2-methylcyclohexyl                                                                             323                                             o-tolyl        cycloheptyl     323                                             o-tolyl        indan-1-yl      343                                             o-tolyl        2-dicyclohexyl  492                                             2-fluorophenyl phenyl          307                                             2-fluorophenyl o-tolyl         321                                             2-fluorophenyl 4-chloro-2-methylphenyl                                                                        356                                             2-fluorophenyl 2-fluorophenyl  325                                             2-fluorophenyl 3-fluorophenyl  325                                             2-fluorophenyl 4-fluorophenyl  325                                             2-fluorophenyl 2,4-difluorophenyl                                                                             343                                             2-fluorophenyl 2-methoxyphenyl 337                                             2-fluorophenyl 3-methoxyphenyl 337                                             2-fluorophenyl 4-methoxyphenyl 337                                             2-fluorophenyl 2,4-dimethoxyphenyl                                                                            367                                             2-fluorophenyl 2-phenoxyphenyl 399                                             2-fluorophenyl 3-phenoxyphenyl 399                                             2-fluorophenyl 4-phenoxyphenyl 399                                             2-fluorophenyl 4-biphenyl      383                                             2-fluorophenyl 4-benzylphenyl  397                                             2-fluorophenyl 4-(trifluoromethoxy)phenyl                                                                     391                                             2-fluorophenyl cyclohexyl      313                                             2-fluorophenyl 2-methylcyclohexyl                                                                             327                                             2-fluorophenyl cycloheptyl     327                                             2-fluorophenyl indan-1-yl      347                                             2-fluorophenyl 2-dicyclohexyl  395                                             2,6-dimethylphenyl                                                                            phenyl          317                                             2,6-dimethylphenyl                                                                            o-tolyl         331                                             2,6-dimethylphenyl                                                                            4-chloro-2-methylphenyl                                                                        366                                             2,6-dimethylphenyl                                                                            2-fluorophenyl  335                                             2,6-dimethylphenyl                                                                            3-fluorophenyl  335                                             2,6-dimethylphenyl                                                                            4-fluorophenyl  335                                             2,6-dimethylphenyl                                                                            2,4-difluorophenyl                                                                             353                                             2,6-dimethylphenyl                                                                            2-methoxyphenyl 347                                             2,6-dimethylphenyl                                                                            3-methoxyphenyl 347                                             2,6-dimethylphenyl                                                                            4-methoxyphenyl 347                                             2,6-dimethylphenyl                                                                            2,4-dimethoxyphenyl                                                                            377                                             2,6-dimethylphenyl                                                                            2-phenoxyphenyl 409                                             2,6-dimethylphenyl                                                                            3-phenoxyphenyl 409                                             2,6-dimethylphenyl                                                                            4-phenoxyphenyl 409                                             2,6-dimethylphenyl                                                                            4-biphenyl      393                                             2,6-dimethylphenyl                                                                            4-benzylphenyl  407                                             2,6-dimethylphenyl                                                                            4-(trifluoromethoxy)phenyl                                                                     401                                             2,6-dimethylphenyl                                                                            cyclohexyl      323                                             2,6-dimethylphenyl                                                                            2-methylcyclohexyl                                                                             337                                             2,6-dimethylphenyl                                                                            cycloheptyl     667                                             2,6-dimethylphenyl                                                                            indan-1-yl      357                                             2,6-dimethylphenyl                                                                            2-dicyclohexyl  406                                             2-phenoxyphenyl                                                                               phenyl          381                                             2-phenoxyphenyl                                                                               o-tolyl         395                                             2-phenoxyphenyl                                                                               4-chloro-2-methylphenyl                                                                        430                                             2-phenoxyphenyl                                                                               2-fluorophenyl  399                                             2-phenoxyphenyl                                                                               3-fluorophenyl  399                                             2-phenoxyphenyl                                                                               4-fluorophenyl  399                                             2-phenoxyphenyl                                                                               2,4-difluorophenyl                                                                             417                                             2-phenoxyphenyl                                                                               2-methoxyphenyl 411                                             2-phenoxyphenyl                                                                               3-methoxyphenyl 411                                             2-phenoxyphenyl                                                                               4-methoxyphenyl 411                                             2-phenoxyphenyl                                                                               2,4-dimethoxyphenyl                                                                            441                                             2-phenoxyphenyl                                                                               2-phenoxyphenyl 473                                             2-phenoxyphenyl                                                                               3-phenoxyphenyl 473                                             2-phenoxyphenyl                                                                               4-phenoxyphenyl 473                                             2-phenoxyphenyl                                                                               4-biphenyl      457                                             2-phenoxyphenyl                                                                               4-benzylphenyl  472                                             2-phenoxyphenyl                                                                               4-(trifluoromethoxy)phenyl                                                                     465                                             2-phenoxyphenyl                                                                               cyclohexyl      387                                             2-phenoxyphenyl                                                                               2-methylcyclohexyl                                                                             401                                             2-phenoxyphenyl                                                                               cycloheptyl     401                                             2-phenoxyphenyl                                                                               indan-1-yl      421                                             2-phenoxyphenyl                                                                               2-dicyclohexyl  470                                             phenyl         phenyl          289                                             phenyl         o-tolyl         303                                             phenyl         4-chloro-2-methylphenyl                                                                        338                                             phenyl         2-fluorophenyl  307                                             phenyl         3-fluorophenyl  307                                             phenyl         4-fluorophenyl  307                                             phenyl         2,4-difluorophenyl                                                                             325                                             phenyl         2-methoxyphenyl 319                                             phenyl         3-methoxyphenyl 319                                             phenyl         4-methoxyphenyl 319                                             phenyl         2,4-dimethoxyphenyl                                                                            349                                             phenyl         2-phenoxyphenyl 381                                             phenyl         3-phenoxyphenyl 381                                             phenyl         4-phenoxyphenyl 381                                             phenyl         4-biphenyl      365                                             phenyl         4-benzylphenyl  379                                             phenyl         4-(trifluoromethoxy)phenyl                                                                     373                                             phenyl         cyclohexyl      295                                             phenyl         2-methylcyclohexyl                                                                             309                                             phenyl         cycloheptyl     309                                             phenyl         indan-1-yl      329                                             phenyl         2-dicyclohexyl  377                                             2,4-difluorophenyl                                                                            phenyl          325                                             2,4-difluorophenyl                                                                            o-tolyl         339                                             2,4-difluorophenyl                                                                            4-chloro-2-methylphenyl                                                                        374                                             2,4-difluorophenyl                                                                            2-fluorophenyl  343                                             2,4-difluorophenyl                                                                            3-fluorophenyl  343                                             2,4-difluorophenyl                                                                            4-fluorophenyl  343                                             2,4-difluorophenyl                                                                            2,4-difluorophenyl                                                                             361                                             2,4-difluorophenyl                                                                            2-methoxyphenyl 355                                             2,4-difluorophenyl                                                                            3-methoxyphenyl 355                                             2,4-difluorophenyl                                                                            4-methoxyphenyl 355                                             2,4-difluorophenyl                                                                            2,4-dimethoxyphenyl                                                                            385                                             2,4-difluorophenyl                                                                            2-phenoxyphenyl 417                                             2,4-difluorophenyl                                                                            3-phenoxyphenyl 417                                             2,4-difluorophenyl                                                                            4-phenoxyphenyl 417                                             2,4-difluorophenyl                                                                            4-biphenyl      401                                             2,4-difluorophenyl                                                                            4-benzylphenyl  415                                             2,4-difluorophenyl                                                                            4-(trifluoromethoxy)phenyl                                                                     409                                             2,4-difluorophenyl                                                                            cyclohexyl      331                                             2,4-difluorophenyl                                                                            2-methylcyclohexyl                                                                             345                                             2,4-difluorophenyl                                                                            cycloheptyl     345                                             2,4-difluorophenyl                                                                            indan-1-yl      365                                             2,4-difluorophenyl                                                                            2-dicyclohexyl  413                                             2,6-diisopropylphenyl                                                                         phenyl          373                                             2,6-diisopropylphenyl                                                                         o-tolyl         387                                             2,6-diisopropylphenyl                                                                         4-chloro-2-methylphenyl                                                                        422                                             2,6-diisopropylphenyl                                                                         2-fluorophenyl  391                                             2,6-diisopropylphenyl                                                                         3-fluorophenyl  391                                             2,6-diisopropylphenyl                                                                         4-fluorophenyl  391                                             2,6-diisopropylphenyl                                                                         2,4-difluorophenyl                                                                             409                                             2,6-diisopropylphenyl                                                                         2-methoxyphenyl 403                                             2,6-diisopropylphenyl                                                                         3-methoxyphenyl 403                                             2,6-diisopropylphenyl                                                                         4-methoxyphenyl 403                                             2,6-diisopropylphenyl                                                                         2,4-dimethoxyphenyl                                                                            434                                             2,6-diisopropylphenyl                                                                         2-phenoxyphenyl 466                                             2,6-diisopropylphenyl                                                                         3-phenoxyphenyl 466                                             2,6-diisopropylphenyl                                                                         4-phenoxyphenyl 466                                             2,6-diisopropylphenyl                                                                         4-biphenyl      450                                             2,6-diisopropylphenyl                                                                         4-benzylphenyl  464                                             2,6-diisopropylphenyl                                                                         4-(trifluoromethoxy)phenyl                                                                     457                                             2,6-diisopropylphenyl                                                                         cyclohexyl      380                                             2,6-diisopropylphenyl                                                                         2-methylcyclohexyl                                                                             394                                             2,6-diisopropylphenyl                                                                         cycloheptyl     394                                             2,6-diisopropylphenyl                                                                         indan-1-yl      414                                             2,6-diisopropylphenyl                                                                         2-dicyclohexyl  462                                             2,4-dimethoxyphenyl                                                                           phenyl          349                                             2,4-dimethoxyphenyl                                                                           o-tolyl         363                                             2 4-dimethoxyphenyl                                                                           4-chloro-2-methylphenyl                                                                        398                                             2,4-dimethoxyphenyl                                                                           2-fluorophenyl  367                                             2,4-dimethoxyphenyl                                                                           3-fluorophenyl  367                                             2,4-dimethoxyphenyl                                                                           4-fluorophenyl  367                                             2,4-dimethoxyphenyl                                                                           2,4-difluorophenyl                                                                             385                                             2,4-dimethoxyphenyl                                                                           2-methoxyphenyl 379                                             2,4-dimethoxyphenyl                                                                           3-methoxyphenyl 379                                             2,4-dimethoxyphenyl                                                                           4-methoxyphenyl 379                                             2,4-dimethoxyphenyl                                                                           2,4-dimethoxyphenyl                                                                            409                                             2,4-dimethoxyphenyl                                                                           2-phenoxyphenyl 441                                             2,4-dimethoxyphenyl                                                                           3-phenoxyphenyl 441                                             2,4-dimethoxyphenyl                                                                           4-phenoxyphenyl 441                                             2,4-dimethoxyphenyl                                                                           4-biphenyl      425                                             2,4-dimethoxyphenyl                                                                           4-benzylphenyl  439                                             2,4-dimethoxyphenyl                                                                           4-(trifluoromethoxy)phenyl                                                                     433                                             2,4-dimethoxyphenyl                                                                           3-trifluoromethylphenyl                                                                        417                                             2,4-dimethoxyphenyl                                                                           cyclohexyl      355                                             2,4-dimethoxyphenyl                                                                           2-methylcyclohexyl                                                                             369                                             3-methoxyphenyl                                                                               phenyl          319                                             3-methoxyphenyl                                                                               o-tolyl         333                                             3-methoxyphenyl                                                                               4-chloro-2-methylphenyl                                                                        368                                             3-methoxyphenyl                                                                               2-fluorophenyl  337                                             3-methoxyphenyl                                                                               3-fluorophenyl  337                                             3-methoxyphenyl                                                                               4-fluorophenyl  337                                             3-methoxyphenyl                                                                               2,4-difluorophenyl                                                                             355                                             3-methoxyphenyl                                                                               2-methoxyphenyl 349                                             3-methoxyphenyl                                                                               3-methoxyphenyl 349                                             3-methoxyphenyl                                                                               4-methoxyphenyl 349                                             3-methoxyphenyl                                                                               2,4-dimethoxyphenyl                                                                            379                                             3-methoxyphenyl                                                                               2-phenoxyphenyl 411                                             3-methoxyphenyl                                                                               3-phenoxyphenyl 411                                             3-methoxyphenyl                                                                               4-phenoxyphenyl 411                                             3-methoxyphenyl                                                                               4-biphenyl      395                                             3-methoxyphenyl                                                                               4-benzylphenyl  409                                             3-methoxyphenyl                                                                               4-(trifluoromethoxy)phenyl                                                                     403                                             3-methoxyphenyl                                                                               3-trifluoromethylphenyl                                                                        387                                             3-methoxyphenyl                                                                               cyclohexyl      625                                             3-methoxyphenyl                                                                               2-methylcyclohexyl                                                                             339                                             4-methoxyphenyl                                                                               phenyl          319                                             4-methoxyphenyl                                                                               o-tolyl         333                                             4-methoxyphenyl                                                                               4-chloro-2-methylphenyl                                                                        368                                             4-methoxyphenyl                                                                               2-fluorophenyl  337                                             4-methoxyphenyl                                                                               3-fluorophenyl  337                                             4-methoxyphenyl                                                                               4-fluorophenyl  337                                             4-methoxyphenyl                                                                               2,4-difluorophenyl                                                                             355                                             4-methoxyphenyl                                                                               2-methoxyphenyl 349                                             4-methoxyphenyl                                                                               3-methoxyphenyl 349                                             4-methoxyphenyl                                                                               4-methoxyphenyl 349                                             4-methoxyphenyl                                                                               2,4-dimethoxyphenyl                                                                            379                                             4-methoxyphenyl                                                                               2-phenoxyphenyl 411                                             4-methoxyphenyl                                                                               3-phenoxyphenyl 411                                             4-methoxyphenyl                                                                               4-phenoxyphenyl 411                                             4-methoxyphenyl                                                                               4-biphenyl      395                                             4-methoxyphenyl                                                                               4-benzylphenyl  409                                             4-methoxyphenyl                                                                               4-(trifluoromethoxy)phenyl                                                                     403                                             4-methoxyphenyl                                                                               3-trifluoromethylphenyl                                                                        387                                             4-methoxyphenyl                                                                               cyclohexyl      625                                             4-methoxyphenyl                                                                               2-methylcyclohexyl                                                                             339                                             2-methoxyphenyl                                                                               phenyl          319                                             2-methoxyphenyl                                                                               o-tolyl         333                                             2-methoxyphenyl                                                                               4-chloro-2-methylphenyl                                                                        368                                             2-methoxyphenyl                                                                               2-fluorophenyl  337                                             2-methoxyphenyl                                                                               3-fluorophenyl  337                                             2-methoxyphenyl                                                                               4-fluorophenyl  337                                             2-methoxyphenyl                                                                               2,4-difluorophenyl                                                                             355                                             2-methoxyphenyl                                                                               2-methoxyphenyl 349                                             2-methoxyphenyl                                                                               3-methoxyphenyl 349                                             2-methoxyphenyl                                                                               4-methoxyphenyl 349                                             2-methoxyphenyl                                                                               2,4-dimethoxyphenyl                                                                            379                                             2-methoxyphenyl                                                                               2-phenoxyphenyl 411                                             2-methoxyphenyl                                                                               3-phenoxyphenyl 411                                             2-methoxyphenyl                                                                               4-phenoxyphenyl 411                                             2-methoxyphenyl                                                                               4-biphenyl      395                                             2-methoxyphenyl                                                                               4-benzylphenyl  409                                             2-methoxyphenyl                                                                               4-(trifluoromethoxy)phenyl                                                                     403                                             2-methoxyphenyl                                                                               3-trifluoromethylphenyl                                                                        387                                             2-methoxyphenyl                                                                               cyclohexyl      625                                             2-methoxyphenyl                                                                               2-methylcyclohexyl                                                                             339                                             ______________________________________                                    

                  TABLE 9                                                          ______________________________________                                          ##STR24##                                                                                                  MS                                                R.sup.3      R.sup.1         (m/z)                                             ______________________________________                                         4-chlorophenyl                                                                              phenyl          338                                               4-chlorophenyl                                                                              o-tolyl         352                                               4-chlorophenyl                                                                              4-chloro-2-methylphenyl                                                                        386                                               4-chlorophenyl                                                                              2-fluorophenyl  356                                               4-chlorophenyl                                                                              3-fluorophenyl  356                                               4-chlorophenyl                                                                              4-fluorophenyl  356                                               4-chlorophenyl                                                                              2,4-difluorophenyl                                                                             374                                               4-chlorophenyl                                                                              2-methoxyphenyl 368                                               4-chlorophenyl                                                                              3-methoxyphenyl 368                                               4-chlorophenyl                                                                              4-methoxyphenyl 368                                               4-chlorophenyl                                                                              2,4-dimethoxyphenyl                                                                            398                                               4-chlorophenyl                                                                              2-phenoxyphenyl 430                                               4-chlorophenyl                                                                              3-phenoxyphenyl 430                                               4-chlorophenyl                                                                              4-phenoxyphenyl 430                                               4-chlorophenyl                                                                              4-biphenyl      414                                               4-chlorophenyl                                                                              4-benzylphenyl  428                                               4-chlorophenyl                                                                              4-(trifluoromethoxy)phenyl                                                                     422                                               4-chlorophenyl                                                                              cyclohexyl      344                                               4-chlorophenyl                                                                              2-methylcyclohexyl                                                                             358                                               phenyl       phenyl          303                                               phenyl       o-tolyl         317                                               phenyl       4-chloro-2-methylphenyl                                                                        352                                               phenyl       2-fluorophenyl  321                                               phenyl       3-fluorophenyl  321                                               phenyl       4-fluorophenyl  321                                               phenyl       2,4-difluorophenyl                                                                             339                                               phenyl       2-methoxyphenyl 333                                               phenyl       3-methoxyphenyl 333                                               phenyl       4-methoxyphenyl 333                                               phenyl       2,4-dimethoxyphenyl                                                                            363                                               phenyl       2-phenoxyphenyl 395                                               phenyl       3-phenoxyphenyl 395                                               phenyl       4-phenoxyphenyl 395                                               phenyl       4-biphenyl      379                                               phenyl       4-benzylphenyl  393                                               phenyl       4-(trifluoromethoxy)phenyl                                                                     387                                               phenyl       3-trifluoromethylphenyl                                                                        371                                               phenyl       cyclohexyl      309                                               phenyl       2-methylcyclohexyl                                                                             323                                               ______________________________________                                    

                  TABLE 10                                                         ______________________________________                                          ##STR25##                                                                                                   MS                                               R.sup.3        R.sup.1        (m/z)                                            ______________________________________                                         o-tolyl        N-methylphenyl 317                                              o-tolyl        4-chloro-N-methylphenyl                                                                       352                                              o-tolyl        N-methylcyclohexyl                                                                            323                                              2-fluorophenyl N-methylphenyl 321                                              2-fluorophenyl 4-chloro-N-methylphenyl                                                                       356                                              2-fluorophenyl N-methylcyclohexyl                                                                            327                                              2,6-dimethylphenyl                                                                            N-methylphenyl 331                                              2,6-dimethylphenyl                                                                            4-chloro-N-methylphenyl                                                                       366                                              2,6-dimethylphenyl                                                                            N-methylcyclohexyl                                                                            337                                              2-phenoxyphenyl                                                                               N-methylphenyl 395                                              2-phenoxyphenyl                                                                               4-chloro-N-methylphenyl                                                                       430                                              2-phenoxyphenyl                                                                               N-methylcyclohexyl                                                                            401                                              phenyl         N-methylphenyl 303                                              phenyl         4-chloro-N-methylphenyl                                                                       338                                              phenyl         N-methylcyclohexyl                                                                            309                                              2,4-difluorophenyl                                                                            N-methylphenyl 339                                              2,4-difluorophenyl                                                                            4-chloro-N-methylphenyl                                                                       374                                              2,4-difluorophenyl                                                                            N-methylcyclohexyl                                                                            345                                              2,6-diisopropylphenyl                                                                         N-methylphenyl 387                                              2,6-diisopropylphenyl                                                                         4-chloro-N-methylphenyl                                                                       422                                              2,6-diisopropylphenyl                                                                         N-methylcyclohexyl                                                                            394                                              2,4-dimethoxyphenyl                                                                           N-methylphenyl 363                                              2,4-dimethoxyphenyl                                                                           4-chloro-N-methylphenyl                                                                       398                                              2,4-dimethoxyphenyl                                                                           N-methylcyclohexyl                                                                            369                                              3-methoxyphenyl                                                                               N-methylphenyl 333                                              3-methoxyphenyl                                                                               4-chloro-N-methylphenyl                                                                       368                                              3-methoxyphenyl                                                                               N-methylcyclohexyl                                                                            339                                              4-methoxyphenyl                                                                               N-methylphenyl 333                                              4-methoxyphenyl                                                                               4-chloro-N-methylphenyl                                                                       368                                              4-methoxyphenyl                                                                               N-methylcyclohexyl                                                                            339                                              2-methoxyphenyl                                                                               N-methylphenyl 333                                              2-methoxyphenyl                                                                               4-chloro-N-methylphenyl                                                                       368                                              2-methoxyphenyl                                                                               N-methylcyclohexyl                                                                            339                                              ______________________________________                                    

                  TABLE 11                                                         ______________________________________                                          ##STR26##                                                                                               MS                                                   R.sup.3        R.sup.1    (m/z)                                                ______________________________________                                         4-chlorophenyl phenyl     338                                                  4-chlorophenyl 4-chlorophenyl                                                                            386                                                  4-chlorophenyl cyclohexyl 358                                                  phenyl         phenyl     317                                                  phenyl         4-chlorophenyl                                                                            352                                                  phenyl         cyclohexyl 323                                                  ______________________________________                                    

The compounds listed in Tables 12-13 can be prepared from 6-chloro-N-substituted nicotinamides compounds and the appropriate amine according to the general procedure above.

                  TABLE 12                                                         ______________________________________                                          ##STR27##                                                                     R.sup.1 X          R.sup.3                                                     ______________________________________                                         o-tolyl            3-trifluoromethylphenyl                                     2-fluorophenyl     3-trifluoromethylphenyl                                     2,6-dimethylphenyl 3-trifluoromethylphenyl                                     2-phenoxyphenyl    3-trifluoromethylphenyl                                     phenyl             3-trifluoromethylphenyl                                     2,4-difluorophenyl 3-trifluoromethylphenyl                                     2,6-diisopropylphenyl                                                                             3-trifluoromethylphenyl                                     2,4-dimethoxyphenyl                                                                               cycloheptyl                                                 2,4-dimethoxyphenyl                                                                               indan-1-yl                                                  2,4-dimethoxyphenyl                                                                               2-dicyclohexyl                                              3-methoxyphenyl    cycloheptyl                                                 3-methoxyphenyl    indan-1-yl                                                  3-methoxyphenyl    2-dicyclohexyl                                              4-methoxyphenyl    cycloheptyl                                                 4-methoxyphenyl    indan-1-yl                                                  4-methoxyphenyl    2-dicyclohexyl                                              2-methoxyphenyl    cycloheptyl                                                 2-methoxyphenyl    indan-1-yl                                                  2-methoxyphenyl    2-dicyclohexyl                                              ______________________________________                                    

                  TABLE 13                                                         ______________________________________                                          ##STR28##                                                                     R.sup.1 X         R.sup.3                                                      ______________________________________                                         4-chlorophenyl    3-trifluoromethylphenyl                                      4-chlorophenyl    cycloheptyl                                                  4-chlorophenyl    indan-1-yl                                                   4-chlorophenyl    2-dicyclohexyl                                               phenyl            cycloheptyl                                                  phenyl            indan-1-yl                                                   phenyl            2-dicyclohexyl                                               ______________________________________                                    

EXAMPLE 20

The following assays were used to characterize the ability of compounds of the invention to inhibit the production of TNF-α and IL-1-β. The second assay measured the inhibition of TNF-α and/or IL-1-β in mice after oral administration of the test compounds. The third assay, a glucagon binding inhibition in vitro assay, can be used to characterize the ability of compounds of the invention to inhibit glucagon binding. The fourth assay, a Cyclooxygenase enzyme (COX-1 and COX-2) inhibition activity in vitro assay, can be used to characterize the ability of compounds of the invention to inhibit COX-1 and/or COX-2. The fifth assay, a Raf-kinase inhibition assay, can be used to characterize the compounds of the invention to inhibit phosphorylation of MEK by activated Raf-kinase.

Lipopolysaccharide-activated monocyte TNF production assay

Isolation of monocytes

Test compounds were evaluated in vitro for the ability to inhibit the production of tumor necrosis factor (TNF) by monocytes activated with bacterial lipopolysaccharide (LPS). Fresh residual source leukocytes (a byproduct of plateletpheresis) were obtained from a local blood bank, and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation on Ficol-Paque Plus (Pharmacia). PBMCs were suspended at 2×10⁶ /ml in DMEM supplemented to contain 2% FCS, 10 mM, 0.3 mg/ml glutamate, 100 U/ml penicillin G and 100 mg/ml streptomycin sulfate (complete media). Cells were plated into Falcon flat bottom, 96 well culture plates (200 μl/well) and cultured overnight at 37° C. and 6% CO₂. Non-adherent cells were removed by washing with 200 μl/well of fresh medium. Wells containing adherent cells (˜70% monocytes) were replenished with 100 μl of fresh medium.

Preparation of test compound stock solutions

Test compounds were dissolved in DMSO. Compound stock solutions were prepared to an initial concentration of 10-50 μM. Stocks were diluted initially to 20-200 μM in complete media. Nine two-fold serial dilutions of each compound were then prepared in complete medium.

Treatment of cells with test compounds and activation of TNF production with lipopolysaccharide

One hundred microliters of each test compound dilution were added to microtiter wells containing adherent monocytes and 100 μl complete medium. Monocytes were cultured with test compounds for 60 min at which time 25 μl of complete medium containing 30 ng/ml lipopolysaccharide from E. coli K532 were added to each well. Cells were cultured an additional 4 hrs. Culture supernatants were then removed and TNF presence in the supernatants was quantified using an ELISA.

TNF ELISA

Flat bottom, 96 well Corning High Binding ELISA plates were coated overnight (4° C.) with 150 μL/well of 3 μg/ml murine anti-human TNF-α MAb (R&D Systems #MAB210). Wells were then blocked for 1 hr at room temperature with 200 μL/well of CaCl₂ -free ELISA buffer supplemented to contain 20 mg/ml BSA (standard ELISA buffer: 20 mM, 150 mM NaCl, 2 mM CaCl₂, 0.15 mM thimerosal, pH 7.4). Plates were washed and replenished with 100 μl of test supernatants (diluted 1:3) or standards. Standards consisted of eleven 1.5-fold serial dilutions from a stock of 1 ng/ml recombinant human TNF (R&D Systems). Plates were incubated at room temperature for 1 hr on orbital shaker (300 rpm), washed and replenished with 100 μl/well of 0.5 μg/ml goat anti-human TNF-α (R&D systems #AB-210-NA) biotinylated at a 4:1 ratio. Plates were incubated for 40 min, washed and replenished with 100 μl/well of alkaline phosphatase-conjugated streptavidin (Jackson ImmunoResearch #016-050-084) at 0.02 μg/ml. Plates were incubated 30 min, washed and replenished with 200 μl/well of 1 mg/ml of p-nitrophenyl phosphate. After 30 min, plates were read at 405 nm on a V_(max) plate reader.

Data analysis

Standard curve data were fit to a second order polynomial and unknown TNF-α concentrations determined from their OD by solving this equation for concentration. TNF concentrations were then plotted vs. test compound concentration using a second order polynomial. This equation was then used to calculate the concentration of test compounds causing a 50% reduction in TNF production.

The following compounds had an IC₅₀ of less than 15 μM:

2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(1-naphthyloxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-(2-methyl-3-pyridyloxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-((3,5-dimethyl-4-isoxazolyl)carbonylamino)pyridine;

2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine; and

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine.

Compounds of the invention can also be shown to inhibit LPS-induced release of IL-1β, IL-6 and/or IL-8 from monocytes by measuring concentrations of IL-1β, IL-6 and/or IL-8 by methods well known to those skilled in the art. In a similar manner to the above described assay involving the LPS induced release of TNF-α from monocytes, compounds of this invention can also be shown to inhibit LPS induced release of IL-1β, IL-6 and/or IL-8 from monocytes by measuring concentrations of IL-1β, IL-6 and/or IL-8 by methods well known to those skilled in the art. Thus, the compounds of the invention may lower elevated levels of TNF-α, IL-1, IL-6, and IL-8 levels. Reducing elevated levels of these inflammatory cytokines to basal levels or below is favorable in controlling, slowing progression, and alleviating many disease states. All of the compounds are useful in the methods of treating disease states in which TNF-α, IL-1β, IL-6, and IL-8 play a role to the full extent of the definition of TNF-α-mediated diseases described herein.

Inhibition of LPS-Induced TNF-α production in mice

Male DBA/1LACJ mice are dosed with vehicle or test compounds in a vehicle (the vehicle consisting of 0.5% tragacanth in 0.03 N HCl) 30 minutes prior to lipopolysaccharide (2 mg/kg, I.V.) injection. Ninety minutes after LPS injection, blood are collected and the serum is analyzed by ELISA for TNF levels.

Selected compounds from the class have shown in vivo activity in a LPS mouse model in which serum levels of TNF-α were reduced in the presence of compounds of this invention.

Compounds of the invention may be shown to have anti-inflammatory properties in animal models of inflammation, including carageenan paw edema, collagen induced arthritis and adjuvant arthritis, such as the carageenan paw edema model (C. A. Winter et al Proc. Soc. Exp. Biol. Med. (1962) vol 111, p 544; K. F. Swingle, in R. A. Scherrer and M. W. Whitehouse, Eds., Antiinflammatory Agents, Chemistry and Pharmacology, Vol. 13-II, Academic, New York, 1974, p. 33) and collagen induced arthritis (D. E. Trentham et al J. Exp. Med. (1977) vol. 146, p 857; J. S. Courtenay, Nature (New Biol.) (1980), Vol 283, p 666).

¹²⁵ I-Glucagon Binding Screen with CHO/hGLUR Cells

The assay is described in WO 97/16442, which is incorporated herein by reference in its entirety.

Reagents

The reagents can be prepared as follows: (a) prepare fresh 1M o-Phenanthroline (Aldrich) (198.2 mg/ml ethanol); (b) prepare fresh 0.5M DTT (Sigma); (c) Protease Inhibitor Mix (1000×): 5 mg leupeptin, 10 mg benzamidine, 40 mg bacitracin and 5 mg soybean trypsin inhibitor per ml DMSO and store aliquots at -20° C.; (d) 250 μM human glucagon (Peninsula): solubilize 0.5 mg vial in 575 μl 0.1N acetic acid (1 μl yields 1 μM final concentration in assay for non-specific binding) and store in aliquots at -20° C.; (e) Assay Buffer: 20 mM Tris (pH 7.8), 1 mM DTT and 3 mM o-phenanthroline; (f) Assay Buffer with 0.1% BSA (for dilution of label only; 0.01% final in assay): 10 μl 10% BSA (heat-inactivated) and 990 μl Assay Buffer; (g) ¹²⁵ I-Glucagon (NEN, receptor-grade, 2200 Ci/mmol): dilute to 50,000 cpm/25 μl in assay buffer with BSA (about 50 pM final concentration in assay).

Harvesting of CHO/hGLUR Cells for Assay

1. Remove media from confluent flask then rinse once each with PBS (Ca, Mg-free) and Enzyme-free Dissociation Fluid (Specialty Media, Inc.).

2. Add 10 ml Enzyme-free Dissoc. Fluid and hold for about 4 min. at 37° C.

3. Gently tap cells free, triturate, take aliquot for counting and centrifuge remainder for 5 min. at 1000 rpm.

4. Resuspend pellet in Assay Buffer at 75000 cells per 100 μl.

Membrane preparations of CHO/hGLUR cells can be used in place of whole cells at the same assay volume. Final protein concentration of a membrane preparation is determined on a per batch basis.

Assay

The determination of inhibition of glucagon binding can be carried out by measuring the reduction of I¹²⁵ -glucagon binding in the presence of compounds of Formula I. The reagents are combined in 120 μL of assay buffer as follows:

    ______________________________________                                                Compound/                                                                              250 μM .sup.125 I-                                                                             CHO/hGLUR                                           Vehicle Glucagon  Glucagon Cells                                        ______________________________________                                         Total    --/5 μl                                                                               --        25 μl                                                                              100 μl                                  Binding                                                                        +        5 μl/--                                                                               --        25 μl                                                                              100 μl                                  Compound                                                                       Nonspecif                                                                               --/5 μl                                                                               1 μl   25 μl                                                                              100 μl                                  ic                                                                             Binding                                                                        ______________________________________                                    

The mixture is incubated for 60 min. at 22° C. on a shaker at 275 rpm. The mixture is filtered over pre-soaked (0.5% polyethylimine (PEI)) GF/C filtermat using an Innotech Harvester or Tomtec Harvester with four washes of ice-cold 20 mM Tris buffer (pH 7.8). The radioactivity in the filters is determined by a gamma-scintillation counter.

Thus, compounds of the invention may also be shown to inhibit the binding of glucagon to glucagon receptors.

Cyclooxygenase Enzyme Activity Assay

The human monocytic leukemia cell line, THP-1, differentiated by exposure to phorbol esters expresses only COX-1; the human osteosarcoma cell line 143B expresses predominantly COX-2. THP-1 cells are routinely cultured in RPMI complete media supplemented with 10% FBS and human osteosarcoma cells (HOSC) are cultured in minimal essential media supplemented with 10% fetal bovine serum (MEM-10%FBS); all cell incubations are at 37° C. in a humidified environment containing 5% CO₂.

COX-1 Assay

In preparation for the COX-1 assay, THP-1 cells are grown to confluency, split 1:3 into RPMI containing 2% FBS and 10 mM phorbol 12-myristate 13-acetate (TPA), and incubated for 48 hours on a shaker to prevent attachment. Cells are pelleted and resuspended in Hank's Buffered Saline (HBS) at a concentration of 2.5×10⁶ cells/mL and plated in 96-well culture plates at a density of 5×10⁵ cells/mL. Test compounds are diluted in HBS and added to the desired final concentration and the cells are incubated for an additional 4 hours. Arachidonic acid is added to a final concentration of 30 mM, the cells incubated for 20 minutes at 37° C., and enzyme activity determined as described below.

COX-2 Assay

For the COX-2 assay, subconfluent HOSC are trypsinized and resuspended at 3×10⁶ cells/mL in MEM-FBS containing 1 ng human IL-1b/mL, plated in 96-well tissue culture plates at a density of 3×10⁴ cells per well, incubated on a shaker for 1 hour to evenly distribute cells, followed by an additional 2 hour static incubation to allow attachment. The media is then replaced with MEM containing 2% FBS (MEM-2% FBS) and 1 ng human IL-1b/mL, and the cells incubated for 18-22 hours. Following replacement of media with 190 mL MEM, 10 mL of test compound diluted in HBS is added to achieve the desired concentration and the cells incubated for 4 hours. The supernatants are removed and replaced with MEM containing 30 mM arachidonic acid, the cells incubated for 20 minutes at 37° C., and enzyme activity determined as described below.

COX Activity Determined

After incubation with arachidonic acid, the reactions are stopped by the addition of 1 N HCl, followed by neutralization with 1 N NaOH and centrifugation to pellet cell debris. Cyclooxygenase enzyme activity in both HOSC and THP-1 cell supernatants is determined by measuring the concentration of PGE₂ using a commercially available ELISA (Neogen #404110). A standard curve of PGE₂ is used for calibration, and commercially available COX-1 and COX-2 inhibitors are included as standard controls.

The following compound exhibits activities in the Cyclooxygenase assay with IC₅₀ values of 10 μM or less: 2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine.

Raf Kinase assay

In vitro Raf kinase activity is measured by the extent of phosphorylation of the substrate MEK (Map kinase/ERK kinase) by activated Raf kinase. Phosphorylated MEK is trapped on a filter and incorporation of radiolabeled phosphate is quantified by scintillation counting.

MATERIALS

Activated Raf is produced by triple transfection of Sf9 cells with baculoviruses expressing "Glu--Glu"-epitope tagged Raf,val¹² -H-Ras, and Lck. The "Glu--Glu"-epitope, Glu-Try-Met-Pro-Met-Glu, was fused to the carboxy-terminus of full length c-Raf.

Catalytically inactive MEK (K97A mutation) is produced in Sf9 cells transfected with a baculovirus expressing c-terminus "Glu--Glu" epitope-tagged K97A MEK1.

Anti "Glu--Glu" antibody was purified from cells grown as described in: Grussenmeyer, et al., Proceedings of the National Academy of Science, U.S.A. pp 7952-7954, 1985.

Column buffer: 20 mM Tris pH=8, 100 mM NaCl, 1 mM EDTA, 2.5 mM EGTA, 10 mM MgCl₂, 2 mM DTT, 0.4 mM AEBSF, 0.1% n-octylglucopyranoside, 1 mM okadeic acid, and 10 μg/mL each of benzamidine, leupeptin, pepstatin, and aprotinin.

5× Reaction buffer: 125 mM HEPES pH=8, 25 mM MgCl₂, 5 mM EDTA, 5 mM Na₃ VO₄, 100 μg/mL BSA.

Enzyme dilution buffer: 25 mM HEPES pH=8, 1 mM EDTA, 1 mM Na₃ VO₄, 400 μg/mL BSA.

Stop solution: 100 mM EDTA, 80 mM sodium pyrophosphate.

Filter plates: Milipore multiscreen # SE3MO78E3, Immobilon-P (PVDF).

METHODS

Protein purification: Sf9 cells were infected with baculovirus and grown as described in Williams, et al., Proceedings of the National Academy of Science, U.S.A. pp 2922-2926, 1992. All subsequent steps were preformed on ice or at 4° C. Cells were pelleted and lysed by sonication in column buffer. Lysates were spun at 17,000×g for 20 min, followed by 0.22 μm filtration. Epitope tagged proteins were purified by chromatography over GammaBind Plus affinity column to which the "Glu--Glu" antibody was coupled. Proteins were loaded on the column followed by sequential washes with two column volumes of column buffer, and eluted with 50 μg/mL Glu-Tyr-Met-Pro-Met-Glu in column buffer.

Raf kinase assay: Test compounds were evaluated using ten 3-fold serial dilutions starting at 10-100 μM. 10 μL of the test inhibitor or control, dissolved in 10% DMSO, was added to the assay plate followed by the addition of 30 μL of the a mixture containing 10 μL 5× reaction buffer, 1 mM ³³ P-γ-ATP (20 μCi/mL), 0.5 μL MEK (2.5 mg/mL), 1 μL 50 mM β-mercaptoethanol. The reaction was started by the addition of 10 μL of enzyme dilution buffer containing 1 mM DTT and an amount of activated Raf that produces linear kinetics over the reaction time course. The reaction was mixed and incubated at room temperature for 90 min. and stopped by the addition of 50 μL stop solution. 90 μL aliquots of this stopped solution were transferred onto GFP-30 cellulose microtiter filter plates (Polyfiltronics), the filter plates washed in four well volumes of 5% phosphoric acid, allowed to dry, and then replenished with 25 μl scintillation cocktail. The plates were counted for ³³ P gamma emission using a TopCount Scintillation Reader.

Accordingly, the compounds of the invention or a pharmaceutical composition thereof are useful for prophylaxis and treatment of rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; graft vs. host reaction; ischemia reperfusion injury; atherosclerosis; brain trauma; Alzheimer's disease; stroke; myocardial infarction; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection. HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), and herpes zoster, all of which are sensitive to TNF-α and/or IL-1 inhibition or glucagon antagonism, will also be positively effected by the compounds and methods of the invention.

The compounds of the present invention may also possess oncolytic characteristics and may be useful for the treatment of cancer. The compounds of the present invention may also block signal transduction by extracellular mitogenic stimuli and oncoproteins through inhibition of Raf kinase.

The compounds of the present invention also may possess analgesic properties and may be useful for the treatment of pain disorders, such as hyperalgesia due to excessive IL-1. The compounds of the present invention may also prevent the production of prostaglandins by inhibition of enzymes in the human arachidonic acid/prostaglandin pathway, including cyclooxygenase (WO 96/03387, incorporated herein by reference in its entirety).

Because of their ability to lower TNF-α and IL-1 concentrations or inhibit glucagon binding to its receptor, the compounds of the invention are also useful research tools for studying the physiology associated with blocking these effects.

The methods of the invention comprise administering an effective dose of a compound of the invention, a pharmaceutical salt thereof, or a pharmaceutical composition of either, to a subject (i.e., an animal, preferably a mammal, most preferably a human) in need of a reduction in the level of TNF-α, IL-1, IL-6, and/or IL-8 levels and/or reduction in plasma glucose levels and/or which subject may be suffering from rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; cancer; bone resorption diseases; graft vs. host reaction; Alzheimer's disease; stroke; myocardial infarction; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection, or which subject is infected by HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), or herpes zoster.

In another aspect, this invention comprises the use of a compound of the invention, or pharmaceutically acceptable salts thereof, in the manufacture of a medicament for the treatment either acutely or chronically of a TNF-α, IL-1β, IL-6, and/or IL-8 mediated disease state, including those described previously. The compounds of the present are also useful in the manufacture of an anti-cancer medicant. The compounds of the present invention are also useful in the manufacture of a medicant to attenuate or prevent signal transduction by extracellular mitogenic stimuli and oncoproteins through inhibition of Raf kinase. Also, the compounds of this invention are useful in the manufacture of a analgesic medicament and a medicament for treating pain disorders, such as hyperalgesia. The compounds of the present invention also are useful in the manufacture of a medicament to prevent the production of prostaglandins by inhibition of enzymes in the human arachidonic acid/prostaglandin pathway.

In still another aspect, this invention provides a pharmaceutical composition comprising an effective TNF-α, IL-1β, IL-6, and/or IL-8 lowering amount and/or effective plasma glucose level lowering amount, and/or effective tumor supressing amount of a compound of the invention and a pharmaceutically acceptable carrier or diluent, and if desired other active ingredients. The compounds of the invention are administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. Therapeutically effective doses of the compounds of the present invention required to arrest the progress or prevent tissue damage associated with the disease are readily ascertained by one of ordinary skill in the art using standard methods.

For the treatment of TNF-α, IL-1β, IL-6, and IL-8 mediated diseases, cancer, and/or hyperglycemia, the compounds of the present invention may be administered orally, parentally, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. The term parenteral as used herein includes, subcutaneous, intravenous, intramuscular, intrasternal, infusion techniques or intraperitoneally.

The dosage regimen for treating a TNF-α, IL-1, IL-6, and IL-8 mediated diseases, cancer, and/or hyperglycemia with the compounds of this invention and/or compositions of this invention is based on a variety of factors, including the type of disease, the age, weight, sex, medical condition of the patient, the severity of the condition, the route of administration, and the particular compound employed. Thus, the dosage regimen may vary widely, but can be determined routinely using standard methods. Dosage levels of the order from about 0.01 mg to 30 mg per kilogram of body weight per day, preferably from about 0.1 mg to 10 mg/kg, more preferably from about 0.25 mg to 1 mg/kg are useful for all methods of use disclosed herein.

The pharmaceutically active compounds of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, including humans and other mammals.

For oral administration, the pharmaceutical composition may be in the form of, for example, a capsule, a tablet, a suspension, or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a given amount of the active ingredient. For example, these may contain an amount of active ingredient from about 1 to 2000 mg, preferably from about 1 to 500 mg, more preferably from about 5 to 150 mg. A suitable daily dose for a human or other mammal may vary widely depending on the condition of the patient and other factors, but, once again, can be determined using routine methods.

The active ingredient may also be administered by injection as a composition with suitable carriers including saline, dextrose, or water. The daily parenteral dosage regimen will be from about 0.1 to about 30 mg/kg of total body weight, preferably from about 0.1 to about 10 mg/kg, and more preferably from about 0.25 mg to 1 mg/kg.

Injectable preparations, such as sterile injectable aqueous or oleaginous suspensions, may be formulated according to the known are using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient such as cocoa butter and polyethylene glycols that are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug.

A suitable topical dose of active ingredient of a compound of the invention is 0.1 mg to 150 mg administered one to four, preferably one or two times daily. For topical administration, the active ingredient may comprise from 0.001% to 10% w/w, e.g., from 1% to 2% by weight of the formulation, although it may comprise as much as 10% w/w, but preferably not more than 5% w/w, and more preferably from 0.1% to 1% of the formulation.

Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin (e.g., liniments, lotions, ointments, creams, or pastes) and drops suitable for administration to the eye, ear, or nose.

For administration, the compounds of this invention are ordinarily combined with one or more adjuvants appropriate for the indicated route of administration. The compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, stearic acid, talc, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulphuric acids, acacia, gelatin, sodium alginate, polyvinylpyrrolidine, and/or polyvinyl alcohol, and tableted or encapsulated for conventional administration. Alternatively, the compounds of this invention may be dissolved in saline, water, polyethylene glycol, propylene glycol, ethanol, corn oil, peanut oil, cottonseed oil, sesame oil, tragacanth gum, and/or various buffers. Other adjuvants and modes of administration are well known in the pharmaceutical art. The carrier or diluent may include time delay material, such as glyceryl monostearate or glyceryl distearate alone or with a wax, or other materials well known in the art.

The pharmaceutical compositions may be made up in a solid form (including granules, powders or suppositories) or in a liquid form (e.g., solutions, suspensions, or emulsions). The pharmaceutical compositions may be subjected to conventional pharmaceutical operations such as sterilization and/or may contain conventional adjuvants, such as preservatives, stabilizers, wetting agents, emulsifiers, buffers etc.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting, sweetening, flavoring, and perfuming agents.

Compounds of the present invention can possess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers as well as in the form of racemic or non-racemic mixtures thereof. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, e.g., by formation of diastereoisomeric salts, by treatment with an optically active acid or base. Examples of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric, and camphorsulfonic acid and then separation of the mixture of diastereoisomers by crystallization followed by liberation of the optically active bases from these salts. A different process for separation of optical isomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Still another available method involves synthesis of covalent diastereoisomeric molecules by reacting compounds of the invention with an optically pure acid in an activated form or an optically pure isocyanate. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compounds of the invention can likewise be obtained by using active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt.

The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. The salts include, but are not limited to, the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methansulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 2-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. Water or oil-soluble or dispersible products are thereby obtained.

Examples of acids that may be employed to from pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Other examples include salts with alkali metals or alkaline earth metals, such as sodium, potassium, calcium or magnesium or with organic bases.

While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more compounds of the invention or other agents. When administered as a combination, the therapeutic agents can be formulated as separate compositions that are given at the same time or different times, or the therapeutic agents can be given as a single composition.

The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims.

From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. 

What is claimed is:
 1. A compound of the formula ##STR29## or a pharmaceutically acceptable salt thereof, wherein X is O, S, S(O), S(O)₂ or NR² ;Y is --C(O)--NR³ R⁴ or --NR⁴ --C(O)--R³ ; R¹ is a cycloalkyl or aryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ -alkyl; provided that the total number of aryl and cycloalkyl radicals in R¹ is 1-3; R² is a hydrogen or alkyl radical; R³ is an aryl radical which is optionally substituted by 1-5 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ -alkyl; provided that the total number of aryl radicals in R³ is 1-3; and provided when Y is --C(O)--NR³ R⁴, then R³ is other than an optionally substituted phenyl or naphthyl having an amino, nitro, cyano or --CO₂ R¹⁹ substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to --NR⁴ --; when Y is --NR⁴ --C(O)--R³ and X is O or S, then R³ is other than an optionally substituted 2-hydroxyphenyl or 2-(alkylcarbonyloxy)phenyl radical; and when R⁴ is a hydrogen radical and X is O or S, then R³ is other than a tert-butylphenyl radical; R⁴ is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or R²⁰ --Z²⁰ -alkyl radical; wherein R¹⁸, R¹⁹ and R²⁰ are each independently a hydrogen, alkyl, haloalkyl, aryl or arylalkyl radical; wherein the aryl radicals of R⁴, R¹⁸, R¹⁹ and R²⁰ are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy; and Z¹⁸, Z¹⁹ and Z²⁰ are each independently --O--, --S--, --S(O)--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; wherein each R²¹ is independently a hydrogen or alkyl radical; R⁵ and R⁶ are each independently a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical; and R⁷ is a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical; provided when Y is --C(O)--NR³ R⁴ and X is O or S, then R⁷ is other than an aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical; and wherein cycloalkyl is a monocyclic, bicyclic or tricyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated or benzo fused; and aryl is a phenyl or biphenyl radical which is optionally benzo fused.
 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, whereinR¹ is a cycloalkyl or aryl radical which is optionally substituted by 1-4 radicals of C₁ -C₆ alkyl, halo, C₁ -C₆ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₆ alkyl; provided that the total number of aryl and cycloalkyl radicals in R¹ is 1-3; R² is a hydrogen or C₁ -C₄ alkyl radical; R³ is an aryl radical which is optionally substituted by 1-5 radicals of C₁ -C₆ alkyl, halo, C₁ -C₆ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ --C₁ -C₆ alkyl; provided that the total number of aryl radicals in R³ is 1-3; R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, C₂ --C₆ alkenyl, C₁ -C₆ haloalkyl of 1-3 halo radicals, C₂ -C₆ haloalkenyl of 1-3 halo radicals, aryl, aryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₁ -C₆ alkyl radical; and wherein R¹⁸, R¹⁹ and R²⁰ are each independently a hydrogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals of R⁴, R¹⁸, R¹⁹ and R²⁰ are optionally substituted by 1-3 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, (C₁ -C₄ alkoxy)carbonylamino, (C₁ -C₄ alkoxy)carbonyl, cyano, halo, azido, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl of 1-3 halo radicals or C₁ -C₄ haloalkoxy of 1-3 halo radicals; and each R²¹ is independently a hydrogen or C₁ -C₄ alkyl radical; R⁵ and R⁶ are each independently a hydrogen, C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, C₁ -C₄ haloalkoxy of 1-3 halo radicals, C₁ -C₄ aminoalkyl, (C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, di(C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, C₁ -C₄ alkylsulfonylamino, aminosulfonyl, C₁ -C₄ alkylaminosulfonyl, di(C₁ -C₄ alkyl)aminosulfonyl, hydroxy, C₁ -C₄ hydroxyalkyl, thiol, C₁ -C₄ alkylthiol, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, C₁ -C₄ alkoxy, (C₁ -C₄ alkoxy)C₁ -C₄ alkyl, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical; and R⁷ is a hydrogen, C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, C₁ -C₄ haloalkoxy of 1-3 halo radicals, C₁ -C₄ aminoalkyl, (C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, di(C₁ -C₄ alkyl)amino-C₁ -C₄ alkyl, aminosulfonyl, C₁ -C₄ alkylaminosulfonyl, di(C₁ -C₄ alkyl)aminosulfonyl, hydroxy, C₁ -C₄ hydroxyalkyl, thiol, C₁ -C₄ alkylthiol, C₁ -C₄ alkylsulfinyl, C₁ -C₄ alkylsulfonyl, C₁ -C₄ alkoxy, (C₁ -C₄ alkoxy)C₁ -C₄ alkyl, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical.
 3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein Y is --NR⁴ --C(O)--R³.
 4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, whereinX is O or NR² ; R¹ is a cycloalkyl or aryl radical which is optionally substituted by 1-4 radicals of C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl; provided that the total number of aryl and cycloalkyl radicals in R¹ is 1-2; wherein each R¹⁸ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, azido, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and R² is a hydrogen or C₁ -C₂ alkyl radical; R³ is an aryl radical which is optionally substituted by 1-5 radicals of C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ --C₁ -C₄ alkyl; provided that the total number of aryl radicals in R³ is 1-2; and wherein each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, aryl, aryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₂ -C₄ alkyl radical; and wherein R²⁰ is a hydrogen, C₁ -C₄ alkyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals of R⁴ and R²⁰ are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and Z²⁰ is --O--, --NH-- or --N(CH₃)--; R⁵ and R⁶ are each independently a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical; and R⁷ is a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di (C₁ -C₄ alkyl)aminocarbonyl radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated or benzo fused.
 5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, whereinR³ is a radical of the formula ##STR30## R¹¹ and R¹³ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹ --Z¹⁹ --; and each R¹² is independently a radical of hydrogen, C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, R³¹ --Z³¹ -- or R³¹ --Z³¹ --C₁ -C₄ alkyl; provided that the combined total number of aryl radicals in R¹¹, R¹² and R¹³ is 0-1; wherein each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z¹⁹ is independently --O--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; wherein each R³¹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z³¹ is independently --O--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; wherein R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, aryl, aryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₂ -C₄ alkyl radical; wherein R²⁰ is a hydrogen, C₁ -C₄ alkyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals of R⁴ and R²⁰ are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and R⁵ and R⁶ are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ -C₂ alkylamino, di(C₁ -C₂ alkyl)amino, hydroxy, methoxy or ethoxy radical; and R⁷ is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-10 ring members, which is optionally partially unsaturated with one double bond or benzo fused.
 6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, whereinR¹ is a radical of the formula ##STR31## wherein R²², R²³, R²⁴, R²⁵ and R²⁶ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl; provided at least one of R²², R²³, R²⁴, R²⁵ and R²⁶ is hydrogen; and provided that the combined total number of aryl radicals in R²², R²³, R²⁴, R²⁵ and R²⁶ is 0-1; and wherein each Z¹⁸ is independently --O--, --S--, --S(O)₂ --, --CO₂ --, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ or --S(O)₂ --NR²¹ --.
 7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, whereinX is NR² ; R² is a hydrogen or methyl radical; R⁴ is a radical of hydrogen, methyl or ethyl radical; and R⁵, R⁶ and R⁷ are each independently a hydrogen radical; and wherein aryl is a phenyl, biphenyl or naphthyl radical.
 8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, whereinR¹¹ and R¹³ are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹ --O--, R¹⁹ --S(O)₂ --, R¹⁹ --O--C(O)--, R¹⁹ --C(O)--, R¹⁹ --NR²¹ --C(O)-- or R¹⁹ --NR²¹ --S(O)₂ --; provided that the combined total number of aryl radicals in R¹¹ and R¹³ is 0-1; each R¹² is independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, aminomethyl, (methylamino)methyl or (dimethylamino)methyl; and wherein each R¹⁹ is independently a hydrogen, methyl, ethyl, trifluoromethyl, phenyl or phenylmethyl radical; wherein the phenyl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, fluoro, chloro, methyl, ethyl, trifluoromethyl or trifluoromethoxy.
 9. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein Y is --C(O)--NR³ R⁴.
 10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, whereinX is O or NR² ; R¹ is a cycloalkyl or aryl radical which is optionally substituted by 1-4 radicals of C₁ -C₄ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl; provided that the total number of aryl and cycloalkyl radicals in R¹ is 1-2; wherein each R¹⁸ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, azido, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and R² is a hydrogen or C₁ -C₂ alkyl radical; R³ is an aryl radical which is optionally substituted by 1-5 radicals of C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹ --Z¹⁹ -- or R¹⁹ --Z¹⁹ --C₁ -C₄ alkyl; provided that the total number of aryl radicals in R³ is 1-2; wherein each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, cyano, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, aryl, aryl-C₁ -C₄ alkyl or R²⁰ --Z²⁰ --C₂ -C₄ alkyl radical; wherein R²⁰ is a hydrogen, C₁ -C₄ alkyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals of R⁴ and R²⁰ are optionally substituted by 1-2 radicals of hydroxy, C₁ -C₄ alkoxy, C₁ -C₄ alkylthiol, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, acetylamino, halo, C₁ -C₄ alkyl, trifluoromethyl or trifluoromethoxy; and Z²⁰ is --O--, --NH-- or --N(CH₃)--; R⁵ and R⁶ are each independently a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, C₁ -C₅ alkanoylamino, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, cyano, azido, nitro, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di(C₁ -C₄ alkyl)aminocarbonyl radical; and R⁷ is a hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C₁ -C₄ hydroxyalkyl, C₁ -C₄ alkoxy, carboxy, (C₁ -C₄ alkoxy)carbonyl, aminocarbonyl, (C₁ -C₄ alkyl)aminocarbonyl or di (C₁ -C₄ alkyl)aminocarbonyl radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated or benzo fused.
 11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, whereinR³ is a radical of the formula ##STR32## R¹¹ and R¹³ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹ --Z¹⁹ --; and each R¹² is independently a radical of hydrogen, C₁ -C₆ alkyl, halo, C₁ -C₄ haloalkyl of 1-3 halo radicals, R³¹ --Z³¹ -- or R³¹ --Z³¹ --C₁ -C₄ alkyl; provided that the combined total number of aryl radicals in R¹¹, R¹² and R¹³ is 0-1; wherein each R¹⁹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z¹⁹ is independently --O--, --S(O)₂ --, --CO₂ --, --C(O)--, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; wherein each R²¹ is independently a hydrogen or methyl radical; wherein each R³¹ is independently a hydrogen, C₁ -C₄ alkyl, trifluoromethyl, aryl or aryl-C₁ -C₄ alkyl radical; wherein the aryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z³¹ is independently --O--, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --; R⁴ is a radical of hydrogen, C₁ -C₆ alkyl, aryl, aryl-C₁ -C₄ alkyl or R²⁰ -Z²⁰ --C₂ -C₄ alkyl radical; and wherein R²⁰ is a hydrogen, C₁ -C₄ alkyl, aryl or aryl-C₁ -C₂ alkyl radical; wherein the aryl radicals of R⁴ and R²⁰ are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and R⁵ and R⁶ are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁ --C₂ alkylamino, di(C₁ -C₂ alkyl)amino, hydroxy, methoxy or ethoxy radical; and R⁷ is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-10 ring members, which is optionally partially unsaturated with one double bond or benzo fused.
 12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, whereinR¹ is a radical of the formula ##STR33## wherein R²², R²³, R²⁴, R²⁵ and R²⁶ are each independently a radical of hydrogen, C₁ -C₄ alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸ --Z¹⁸ -- or R¹⁸ --Z¹⁸ --C₁ -C₄ alkyl; provided at least one of R²², R²³, R²⁴, R²⁵ and R²⁶ is hydrogen; and provided that the combined total number of aryl radicals in R²², R²³, R²⁴, R²⁵ and R²⁶ is 0-1; and each Z¹⁸ is independently --O--, --S--, --S(O)₂ --, --CO₂ --, --NR²¹ --, --NR²¹ --C(O)--, --C(O)--NR²¹ --, --NR²¹ --S(O)₂ -- or --S(O)₂ --NR²¹ --.
 13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, whereinX is NR² ; R² is a hydrogen or methyl radical; R⁴ is a radical of hydrogen, methyl or ethyl radical; and R⁵, R⁶ and R⁷ are each independently a hydrogen radical; andwherein aryl is a phenyl, biphenyl or naphthyl radical.
 14. The compound of claim 13 or a pharmaceutically acceptable salt thereof, whereinR¹¹ and R¹³ are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹ --O--, R¹⁹ --S(O)₂ --, R¹⁹ --O--C(O)--, R¹⁹ --C(O)--, R¹⁹ --NR²¹ --C(O)-- or R¹⁹ --NR²¹ --S(O)₂ --; provided when U is C--R¹³ and V and W are each C--R¹², R¹¹ and R¹³ are each other than a nitro, cyano, carboxy or alkoxycarbonyl radical; and provided that the combined total number of aryl radicals in R¹¹ and R¹³ is 0-1; each R¹² is independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, aminomethyl, (methylamino)methyl or (dimethylamino)methyl; and wherein each R¹⁹ is independently a hydrogen, methyl, ethyl, trifluoromethyl, phenyl or phenylmethyl radical; wherein the phenyl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, fluoro, chloro, methyl, ethyl, trifluoromethyl or trifluoromethoxy.
 15. The compound of claim 1 which is:2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine; 2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine; 2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino) pyridine; 2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino) pyridine; 2-(2,4-dimethylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine; 2-(2,4-dimethylphenoxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino) pyridine; 2-(2,6-dimethyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino) pyridine; 2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine; 2-(2-methylphenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine; 2-(2-methylphenoxy)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine; 2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine; 2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine; 2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine; 2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine; 2-(2-methylphenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine; 2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine; 2-(1-naphthyloxy)-5-(2-methylphenylcarbonylamino) pyridine; 2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino) pyridine; 2-(1-naphthyloxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine; 2-(2-methyl-4-chlorophenylthiol)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenylthiol)-5-(2,6-dimethylphenylcarbonylamino)pyridine; 2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino) pyridine; 2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino) pyridine; 2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine; 2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenylamino)-5-(2-fluorophenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenylamino)-5-(2-chlorophenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenylamino)-5-(2,6-dichlorophenylcarbonylamino)pyridine; 2-(2,4-dimethylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine; 2-(2-methylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine; 2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine; 2-(2,4-dimethylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine; 2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine; 2-(2-methyl-4-chlorophenylamino)-5-(2,6-dimethylphenyl carbonylamino)pyridine; or 2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine.
 16. A pharmaceutical composition comprising a compound of any one of claims 1 to 15 and a pharmaceutically acceptable carrier.
 17. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a compound of any one of claims 1 to
 15. 18. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a composition of claim
 16. 